Devices for therapeutic nasal neuromodulation and associated methods and systems

ABSTRACT

Devices for therapeutic nasal neuromodulation and associated systems and methods are disclosed herein. A system for therapeutic neuromodulation in a nasal region configured in accordance with embodiments of the present technology can include, for example, a shaft and a therapeutic element at a distal portion of the shaft. The shaft can locate the distal portion intraluminally at a target site inferior to a patient&#39;s sphenopalatine foramen. The therapeutic element can include an energy delivery element configured to therapeutically modulate postganglionic parasympathetic nerves at microforamina of a palatine bone of the human patient for the treatment of rhinitis or other indications. In other embodiments, the therapeutic element can be configured to therapeutically modulate nerves that innervate the frontal, ethmoidal, sphenoidal, and maxillary sinuses for the treatment of chronic sinusitis.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority to U.S. Provisional PatentApplication No. 62/160,289, filed May 12, 2015, which is incorporated byreference herein in its entirety.

TECHNICAL FIELD

The present technology relates generally to devices, systems, andmethods for therapeutically modulating nerves in or associated with anasal region of a patient. In particular, various embodiments of thepresent technology are related to therapeutic neuromodulation systemsand methods for the treating rhinitis and other indications.

BACKGROUND

Rhinosinusitis is characterized as an inflammation of the mucousmembrane of the nose and refers to a group of conditions, includingallergic rhinitis, non-allergic rhinitis, chronic rhinitis, chronicsinusitis, and medical resistant rhinitis. Symptoms of rhinosinusitisinclude nasal blockage, obstruction, congestion, nasal discharge (e.g.,rhinorrhea and/or posterior nasal drip), facial pain, facial pressure,and/or reduction or loss of smell. Allergic rhinitis can include furthersymptoms, such as sneezing, watery rhinorrhea, nasal itching, and itchyor watery eyes. Severe rhinitis can lead to exacerbation of coexistingasthma, sleep disturbances, and impairment of daily activities.Depending on the duration and type of systems, rhinosinusitis can fallwithin four subtypes: acute rhinosinusitis, recurrent rhinosinusitis,chronic rhinosinusitis with nasal polyposis (i.e., soft, non-cancerousgrowths on the lining of the nasal passages or sinuses), and chronicrhinosinusitis without nasal polyposis. Acute rhinosinusitis refers tosymptoms lasting for less than twelve weeks, whereas chronicrhinosinusitis (with and without nasal polyposis) refers to symptomslasting longer than twelve weeks. Recurrent rhinosinusitis refers tofour or more episodes of acute rhinosinusitis within a twelve-monthperiod, with resolution of symptoms between each episode.

There are numerous environmental and biological causes ofrhinosinusitis. Non-allergic rhinosinusitis, for example, can be causedby environmental irritants (e.g., exhaust fumes, cleaning solutions,latex, perfume, dust, etc.), medications (e.g., NSAIDs, oralcontraceptives, blood pressure medications including ACE inhibitors,antidepressants, etc.), foods (e.g., alcoholic beverages, spicy foods,etc.), hormonal changes (e.g., pregnancy and menstruation), and/or nasalseptum deviation. Triggers of allergic rhinitis can include exposure toseasonal allergens (e.g., exposure to environmental allergens at similartimes each year), perennial allergens that occur any time of year (e.g.,dust mites, animal dander, molds, etc.), and/or occupational allergens(e.g., certain chemicals, grains, latex, etc.).

The treatment of rhinosinusitis can include a general avoidance ofrhinitis triggers, nasal irrigation with a saline solution, and/or drugtherapies. Pharmaceutical agents prescribed for rhinosinusitis include,for example, oral H1 antihistamines, topical nasal H1 antihistamines,topical intranasal corticosteroids, systemic glucocorticoids, injectablecorticosteroids, anti-leukotrienes, nasal or oral decongestants, topicalanticholinergic, chromoglycate, and/or anti-immunoglobulin E therapies.However, these pharmaceutical agents have limited efficacy (e.g., 17%higher than placebo or less) and undesirable side effects, such assedation, irritation, impairment to taste, sore throat, dry nose,epistaxis (i.e., nose bleeds), and/or headaches. Immunotherapy,including sublingual immunotherapy (“SLIT”), has also been used to treatallergic rhinitis by desensitizing the patient to particular allergensby repeated administration of an allergen extract. However,immunotherapy requires an elongated administration period (e.g., 3-5years for SLIT) and may result in numerous side effects, including painand swelling at the site of the injection, urticarial (i.e., hives),angioedema, asthma, and anaphylaxis.

Surgical interventions have also been employed in an attempt to treatpatients with drug therapy resistant, severe rhinitis symptoms. In the1960's through 1980's, surgeries were performed to sever parasympatheticnerve fibers in the vidian canal to decrease parasympathetic tone in thenasal mucosa. More recent attempts at vidian neurectomies were found tobe 50-88% effective for the treatment of rhinorrhea, with otherancillary benefits including improvements in symptoms of sneezing andnasal obstruction. These symptomatic improvements have also beencorrelated to histologic mucosal changes with reductions in stromaledema, eosinophilic cellular infiltration, mast cell levels, andhistamine concentrations in denervated mucosa. However, despite theclinical and histologic efficacy of vidian neurectomy, resecting thevidian nerve failed to gain widespread acceptance largely due to themorbidities associated with its lack of anatomic and autonomicselectivity. For example, the site of neurectomy includes preganglionicsecretomotor fibers to the lacrimal gland, and therefore the neurectomyoften resulted in the loss of reflex tearing, i.e., lacrimation, whichin severe cases can cause vision loss. Due to such irreversiblecomplications, this technique was soon abandoned. Further, due passageof postganglionic pterygopalatine fibers through the retro-orbitalplexus, the position of the vidian neurectomy relative to the target endorgan (i.e., the nasal mucosa) may result in re-innervation via theautonomic plexus and otic ganglion projections traveling with theaccessory meningeal artery.

The complications associated with vidian neurectomies are generallyattributed to the nonspecific site of autonomic denervation.Consequently, surgeons have recently shifted the site of the neurectomyto postganglionic parasympathetic rami that may have the samephysiologic effect as a vidian neurectomy, while avoiding collateralinjury to the lacrimal and sympathetic fibers. For example, surgeons inJapan have performed transnasal inferior turbinate submucosal resectionsin conjunction with resections of the posterior nasal nerves (“PNN”),which are postganglionic neural pathways located further downstream thanthe vidian nerve. (See, Kobayashi T, Hyodo M, Nakamura K, Komobuchi H,Honda N, Resection of peripheral branches of the posterior nasal nervecompared to conventional posterior neurectomy in severe allergicrhinitis. Auris Nasus Larynx. 2012 Feb. 15; 39:593-596.) The PNNneurectomies are performed at the sphenopalatine foramen, where the PNNis thought to enter the nasal region. These neurectomies are highlycomplex and laborious because of a lack of good surgical markers foridentifying the desired posterior nasal nerves and, even if the desirednerves are located, resection of the nerves is very difficult becausethe nerves must be separated from the surrounding vasculature (e.g., thesphenopalatine artery).

BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of the present technology can be better understood withreference to the following drawings. The components in the drawings arenot necessarily to scale. Instead, emphasis is placed on illustratingclearly the principles of the present technology. For ease of reference,throughout this disclosure identical reference numbers may be used toidentify identical or at least generally similar or analogous componentsor features.

FIG. 1A is a cut-away side view illustrating the anatomy of a lateralnasal wall.

FIG. 1B is an enlarged side view of the nerves of the lateral nasal wallof FIG. 1A.

FIG. 1C is a front view of a left palatine bone illustrating geometry ofmicroforamina in the left palatine bone.

FIG. 2 is a partially schematic view of a therapeutic neuromodulationsystem for therapeutically modulating nerves in a nasal region inaccordance with an embodiment of the present technology.

FIGS. 3A-3E are partial cut-away side views illustrating variousapproaches for delivering a distal portion of a therapeuticneuromodulation device to a target site within a nasal region inaccordance with embodiments of the present technology.

FIG. 4 is an isometric view of a distal portion of a therapeuticneuromodulation device configured in accordance with an embodiment ofthe present technology.

FIGS. 5A-5G are isometric views of electrode configurations oftherapeutic neuromodulation devices for therapeutic neuromodulation inaccordance with embodiments of the present technology.

FIGS. 6A and 6B are partially schematic diagrams illustrating electrodeconfigurations at a distal portion of a therapeutic neuromodulationdevice for nerve detection configured in accordance with embodiments ofthe present technology.

FIG. 7 is a graph illustrating threshold levels of electricalconductivity of nasal tissue with respect to temperature.

FIGS. 8 and 9 are isometric views of a distal portion of a therapeuticneuromodulation device configured in accordance with an embodiment ofthe present technology.

FIG. 10A is an isometric view of a distal portion of a therapeuticneuromodulation device configured in accordance with another embodimentof the present technology, and FIG. 10B is an isometric viewillustrating the therapeutic neuromodulation device of FIG. 10A at atreatment site.

FIGS. 11A-11D are isometric views illustrating a distal portion of atherapeutic neuromodulation device configured in accordance with yetanother embodiment of the present technology.

FIG. 12 is a side view of a distal portion of a therapeuticneuromodulation device configured in accordance with a furtherembodiment of the present technology.

FIG. 13 is a side view of a distal portion of a therapeuticneuromodulation device configured in accordance with a still furtherembodiment of the present technology.

FIG. 14 is an isometric side view of a distal portion of a therapeuticneuromodulation device configured in accordance with an additionalembodiment of the present technology.

FIG. 15 is an isometric side view of a distal portion of a therapeuticneuromodulation device configured in accordance with an additionalembodiment of the present technology.

FIG. 16 is a cross-sectional side view of a distal portion of atherapeutic neuromodulation device configured in accordance with anadditional embodiment of the present technology.

FIG. 17 is a cross-sectional side view of a distal portion of atherapeutic neuromodulation device configured in accordance with anadditional embodiment of the present technology.

FIG. 18 is a cross-sectional side view of a distal portion of atherapeutic neuromodulation device configured in accordance with anadditional embodiment of the present technology.

FIG. 19 is a side view of a distal portion of a therapeuticneuromodulation device configured in accordance with an additionalembodiment of the present technology.

FIG. 20 is a partial cut-away side view illustrating target sitesproximate to ostia of nasal sinuses for a therapeutic neuromodulationdevice configured in accordance with embodiments of the presenttechnology.

DETAILED DESCRIPTION

The present technology is generally directed to devices for therapeuticnasal neuromodulation and associated systems and methods. The discloseddevices are configured to provide an accurate and localized non-invasiveapplication of energy to disrupt the parasympathetic motor sensoryfunction in the nasal region. Specific details of several embodiments ofthe present technology are described herein with reference to FIGS.1A-20. Although many of the embodiments are described with respect todevices, systems, and methods for therapeutically modulating nerves inthe nasal region for the treatment of rhinitis, other applications andother embodiments in addition to those described herein are within thescope of the present technology. For example, at least some embodimentsof the present technology may be useful for the treatment of otherindications, such as the treatment of chronic sinusitis and epitaxis. Itshould be noted that other embodiments in addition to those disclosedherein are within the scope of the present technology. Further,embodiments of the present technology can have different configurations,components, and/or procedures than those shown or described herein.Moreover, a person of ordinary skill in the art will understand thatembodiments of the present technology can have configurations,components, and/or procedures in addition to those shown or describedherein and that these and other embodiments can be without several ofthe configurations, components, and/or procedures shown or describedherein without deviating from the present technology.

With regard to the terms “distal” and “proximal” within thisdescription, unless otherwise specified, the terms can referencerelative positions of portions of a therapeutic neuromodulation deviceand/or an associated delivery device with reference to an operatorand/or a location within the nasal cavity. For example, in referring toa delivery catheter suitable to deliver and position various prostheticvalve devices described herein, “proximal” can refer to a positioncloser to the operator of the device or access point at the entrancepoint of a patient's nostril, and “distal” can refer to a position thatis more distant from the operator of the device or further from theaccess point at the entrance of the patient's nostril. Additionally,posterior, anterior, inferior and superior are used in accordance withstandard medical terminology.

As used herein, the terms “therapeutic modulation” of nerves and“therapeutic neuromodulation” refer to the partial or completeincapacitation or other effective disruption of neural activity,including partial or complete ablation of nerves. Therapeuticneuromodulation, for example, can include partially or completelyinhibiting, reducing, and/or blocking neural communication along neuralfibers.

Anatomy of the Nasal Cavity

FIG. 1A is a cut-away side view illustrating the anatomy of a lateralnasal wall, and FIG. 1B is an enlarged side view of the nerves of thelateral nasal wall of FIG. 1A. The sphenopalatine foramen (“SPF”; FIG.1A) is an opening or conduit defined by the palatine bone and thesphenoid bone through which the sphenopalatine vessels and the posteriorsuperior nasal nerves travel into the nasal cavity. More specifically,the orbital and sphenoidal processes of the perpendicular plate of thepalatine bone define the sphenopalatine notch, which is converted intothe SPF by the articulation with the surface of the body of the sphenoidbone.

The location of the SPF is highly variable within the posterior regionof the lateral nasal cavity, which makes it difficult to visually locatethe SPF. Typically, the SPF is located in the middle meatus (“MM”; FIG.1A); however, anatomical variations also result in the SPF being locatedin the superior meatus (“SM”; FIG. 1A) or at the transition of thesuperior and middle meatuses. In certain individuals, for example, theinferior border of the SPF has been measured at about 19 mm above thehorizontal plate of the palatine bone (i.e., the nasal sill), which isabout 13 mm above the horizontal lamina of the inferior turbinate (“IT”;FIG. 1A), and the average distance from the nasal sill to the SPF isabout 64.4 mm, resulting in an angle of approach from the nasal sill tothe SPA of about 11.4°. However, studies to measure the precise locationof the SPF are of limited practical application due to the widevariation of its location.

The anatomical variations of the SPF are expected to correspond toalterations of the autonomic and vascular pathways traversing into thenasal cavity. In general, it is thought that the posterior nasal nerves(also referred to as lateral posterior superior nasal nerves) branchfrom the pterygopalatine ganglion (“PPG”; also referred to as thesphenopalatine ganglion; FIG. 1A) through the SPF to enter the lateralnasal wall of the nasal cavity, and the sphenopalatine artery passesfrom the pterygopalatine fossa through the SPF on the lateral nasalwall. The sphenopalatine artery branches into two main portions: theposterior lateral nasal branch and the posterior septal branch. The mainbranch of the posterior lateral nasal artery travels inferiorly into theinferior turbinate IT (e.g., between about 1.0 mm and 1.5 mm from theposterior tip of the inferior turbinate IT), while another branch entersthe middle turbinate MT and branches anteriorly and posteriorly.

Beyond the SPF, studies have shown that over 30% of human patients haveone or more accessory foramen that also carries arteries and nerves intothe nasal cavity. The accessory foramena are typically smaller than theSPF and positioned inferior to the SPF. For example, there can be one,two, three or more branches of the posterior nasal artery and posteriornasal nerves that extend through corresponding accessory foramen. Thevariability in location, size, and quantity associated with theaccessory foramen and the associated branching arteries and nerves thattravel through the accessory foramen gives rise to a great deal ofuncertainty regarding the positions of the vasculature and nerves of thesphenopalatine region. Furthermore, the natural anatomy extending fromthe SPF often includes deep inferior and/or superior grooves that carryneural and arterial pathways, which make it difficult to locate arterialand neural branches. For example the grooves can extend more than 5 mmlong, more than 2 mm wide, and more than 1 mm deep, thereby creating apath significant enough to carry both arteries and nerves. Thevariations caused by the grooves and the accessory foramen in thesphenopalatine region make locating and accessing the arteries andnerves (positioned posterior to the arteries) extremely difficult forsurgeons.

Recent microanatomic dissection of the pterygopalatine fossa (PPF) havefurther evidenced the highly variable anatomy of the region surroundingthe SPF, showing that a multiplicity of efferent rami that project fromthe pterygopalatine ganglion (“PPG”; FIG. 1) to innervate the orbit andnasal mucosa via numerous groups of small nerve fascicles, rather thanan individual postganglionic autonomic nerves (e.g., the posterior nasalnerve). Studies have shown that at least 87% of humans havemicroforamina and micro rami in the palatine bone. FIG. 1C, for example,is a front view of a left palatine bone illustrating geometry ofmicroforamina and micro rami in a left palatine bone. In FIG. 1C, thesolid regions represent nerves traversing directly through the palatinebone, and the open circles represent nerves that were associated withdistinct microforamina. Indeed, FIG. 1C illustrates that a medialportion of the palatine bone can include at least 25 accessoryposterolateral nerves.

The respiratory portion of the nasal cavity mucosa is composed of a typeof ciliated pseudostratified columnar epithelium with a basementmembrane. Nasal secretions (e.g., mucus) are secreted by goblet cells,submucosal glands, and transudate from plasma. Nasal seromucous glandsand blood vessels are highly regulated by parasympathetic innervationderiving from the vidian and other nerves. Parasympathetic (cholinergic)stimulation through acetylcholine and vasoactive intestinal peptidegenerally results in mucus production. Accordingly, the parasympatheticinnervation of the mucosa is primarily responsible submucosal glandactivation/hyper activation, venous engorgement (e.g., congestion), andincreased blood flow to the blood vessels lining the nose. Accordingly,severing or modulating the parasympathetic pathways that innervate themucosa are expected to reduce or eliminate the hyper activation of thesubmucosal glands and engorgement of vessels that cause symptomsassociated with rhinosinusitis and other indications.

As discussed above, postganglionic parasympathetic fibers that innervatethe nasal mucosa (i.e., posterior superior nasal nerves) were thought totravel exclusively through the SPF as a sphenopalatine neurovascularbundle. The posterior nasal nerves are branches of the maxillary nervethat innervate the nasal cavity via a number of smaller medial andlateral branches extending through the mucosa of the superior and middleturbinates ST, MT (i.e., nasal chonchea) and to the nasal septum. Thenasopalatine nerve is generally the largest of the medial posteriorsuperior nasal nerves. It passes antero-inferiorly in a groove on thevomer to the floor of the nasal cavity. From here, it passes through theincisive fossa of the hard palate and communicates with the greaterpalatine nerve to supply the mucosa of the hard palate. The posteriorsuperior nasal nerves pass through the pterygopalatine ganglion PPGwithout synapsing and onto the maxillary nerve via its ganglionicbranches.

Based on the understanding that the posterior nasal nerves exclusivelytraverse the SPF to innervate the nasal mucosa, surgeries have beenperformed to selectively sever the posterior nasal nerve as it exits theSPF. However, as discussed above, the sinonasal parasympathetic pathwayactually comprises individual rami project from the pterygopalatineganglion (PPG) to innervate the nasal mucosa via multiple small nervefascicles (i.e., accessory posterolateral nerves), not a single branchextending through the SPF. These rami are transmitted through multiplefissures, accessory foramina, and microforamina throughout the palatinebone and may demonstrate anastomotic loops with both the SPF and otheraccessory nerves. Thus, if only the parasympathetic nerves traversingthe SPF were severed, almost all patients (e.g., 90% of patients ormore) would retain intact accessory secretomotor fibers to theposterolateral mucosa, which would result in the persistence of symptomsthe neurectomy was meant to alieve.

Accordingly, embodiments of the present technology are configured totherapeutically modulate nerves at precise and focused treatment sitescorresponding to the sites of rami extending through fissures, accessoryforamina, and microforamina throughout the palatine bone (e.g., targetregion T shown in FIG. 1B). In certain embodiments, the targeted nervesare postganglionic parasympathetic nerves that go on to innervate thenasal mucosa. This selective neural treatment is also expected todecrease the rate of postoperative nasal crusting and dryness because itallows a clinician to titrate the degree of anterior denervation throughjudicious sparing of the rami orbitonasalis. Furthermore, embodiments ofthe present technology are also expected to maintain at least somesympathetic tone by preserving a portion of the sympatheticcontributions from the deep petrosal nerve and internal maxillaryperiarteriolar plexi, leading to improved outcomes with respect to nasalobstruction. In addition, embodiments of the present technology areconfigured to target a multitude of parasympathetic neural entrylocations (e.g., accessory foramen, fissures, and microforamina) to thenasal region to provide for a complete resection of all anastomoticloops, thereby reducing the rate of long-term re-innervation.

Selected Embodiments of Systems for Therapeutic Nasal Neuromodulationand Neural Mapping

FIG. 2 is a partially schematic view of a therapeutic neuromodulationsystem 200 (“system 200”) for therapeutically modulating nerves in anasal region in accordance with an embodiment of the present technology.The system 200 includes a therapeutic neuromodulation catheter or device202, a console 204, and a cable 206 extending therebetween. Thetherapeutic neuromodulation device 202 includes a shaft 208 having aproximal portion 208 a, a distal portion 208 b, a handle 210 at aproximal portion 208 a of the shaft 208, and a therapeutic assembly orelement 212 at the distal portion 208 b of the shaft 208. The shaft 208is configured to locate the distal portion 208 b intraluminally at atreatment or target site within a nasal region proximate topostganglionic parasympathetic nerves that innervate the nasal mucosa.The target site may be a region, volume, or area in which the targetnerves are located and may differ in size and shape depending upon theanatomy of the patient. For example, the target site may be a 3 cm areainferior to the SPF. In other embodiments, the target site may belarger, smaller, and/or located elsewhere in the nasal cavity to targetthe desired neural fibers. The therapeutic assembly 212 can include atleast one energy delivery element 214 configured to therapeuticallymodulate the postganglionic parasympathetic nerves. In certainembodiments, for example, the therapeutic assembly 212 cantherapeutically modulate the postganglionic parasympathetic nervesbranching from the pterygopalatine ganglion and innervating the nasalregion and nasal mucosa, such as parasympathetic nerves (e.g., theposterior nasal nerves) traversing the SPF, accessory foramen, andmicroforamina of a palatine bone.

As shown in FIG. 2, the therapeutic assembly 212 includes at least oneenergy delivery element 214 configured to provide therapeuticneuromodulation to the target site. In certain embodiments, for example,the energy delivery element 214 can include one or more electrodesconfigured to apply electromagnetic neuromodulation energy (e.g., RFenergy) to target sites. In other embodiments, the energy deliveryelement 214 can be configured to provide therapeutic neuromodulationusing various other modalities, such as cryotherapeutic cooling,ultrasound energy (e.g., high intensity focused ultrasound (“HIFU”)energy), microwave energy (e.g., via a microwave antenna), directheating, high and/or low power laser energy, mechanical vibration,and/or optical power. In further embodiments, the therapeutic assembly212 can be configured to deliver chemicals or drugs to the target siteto chemically ablate or embolize the target nerves. For example, thetherapeutic assembly 212 can include a needle applicator extendingthrough an access portion of the shaft 208 and/or a separate introducer,and the needle applicator can be configured to inject a chemical intothe target site to therapeutically modulate the target nerves, such asbotox, alcohol, guanethidine, ethanol, phenol, a neurotoxin, or anothersuitable agent selected to alter, damage, or disrupt nerves.

In certain embodiments, the therapeutic assembly 212 can include one ormore sensors (not shown), such as one or more temperature sensors (e.g.,thermocouples, thermistors, etc.), impedance sensors, and/or othersensors. The sensor(s) and/or the energy delivery element 214 can beconnected to one or more wires (not shown; e.g., copper wires) extendingthrough the shaft 208 to transmit signals to and from the sensor(s)and/or convey energy to the energy delivery element 214.

The therapeutic neuromodulation device 202 can be operatively coupled tothe console 204 via a wired connection (e.g., via the cable 206) and/ora wireless connection. The console 204 can be configured to control,monitor, supply, and/or otherwise support operation of the therapeuticneuromodulation device 202. The console 204 can further be configured togenerate a selected form and/or magnitude of energy for delivery totissue or nerves at the target site via the therapeutic assembly 212,and therefore the console 204 may have different configurationsdepending on the treatment modality of the therapeutic neuromodulationdevice 202. For example, when therapeutic neuromodulation device 202 isconfigured for electrode-based, heat-element-based, and/ortransducer-based treatment, the console 204 can include an energygenerator 216 configured to generate RF energy (e.g., monopolar,bipolar, or multi-polar RF energy), pulsed electrical energy, microwaveenergy, optical energy, ultrasound energy (e.g.,intraluminally-delivered ultrasound and/or HIFU), direct heat energy,radiation (e.g., infrared, visible, and/or gamma radiation), and/oranother suitable type of energy. When the therapeutic neuromodulationdevice 202 is configured for cryotherapeutic treatment, the console 204can include a refrigerant reservoir (not shown), and can be configuredto supply the therapeutic neuromodulation device 202 with refrigerant.Similarly, when the therapeutic neuromodulation device 202 is configuredfor chemical-based treatment (e.g., drug infusion), the console 204 caninclude a chemical reservoir (not shown) and can be configured to supplythe therapeutic neuromodulation device 202 with one or more chemicals.

As further shown in FIG. 2, the system 200 can further include acontroller 218 communicatively coupled to the therapeuticneuromodulation device 202. In the illustrated embodiment, thecontroller 218 is housed in the console 204. In other embodiments, thecontroller 218 can be carried by the handle 210 of the therapeuticneuromodulation device 202, the cable 206, an independent component,and/or another portion of the system 200. The controller 218 can beconfigured to initiate, terminate, and/or adjust operation of one ormore components (e.g., the energy delivery element 214) of thetherapeutic neuromodulation device 202 directly and/or via the console204. The controller 218 can be configured to execute an automatedcontrol algorithm and/or to receive control instructions from anoperator (e.g., a clinician). For example, the controller 218 and/orother components of the console 204 (e.g., memory) can include acomputer-readable medium carrying instructions, which when executed bythe controller 218, causes the therapeutic assembly 202 to performcertain functions (e.g., apply energy in a specific manner, detectimpedance, detect temperature, detect nerve locations or anatomicalstructures, etc.). A memory includes one or more of various hardwaredevices for volatile and non-volatile storage, and can include bothread-only and writable memory. For example, a memory can comprise randomaccess memory (RAM), CPU registers, read-only memory (ROM), and writablenon-volatile memory, such as flash memory, hard drives, floppy disks,CDs, DVDs, magnetic storage devices, tape drives, device buffers, and soforth. A memory is not a propagating signal divorced from underlyinghardware; a memory is thus non-transitory.

Further, the console 204 can be configured to provide feedback to anoperator before, during, and/or after a treatment procedure viaevaluation/feedback algorithms 220. For example, the evaluation/feedbackalgorithms 220 can be configured to provide information associated withthe temperature of the tissue at the treatment site, the location ofnerves at the treatment site, and/or the effect of the therapeuticneuromodulation on the nerves at the treatment site. In certainembodiments, the evaluation/feedback algorithm 220 can include featuresto confirm efficacy of the treatment and/or enhance the desiredperformance of the system 200. For example, the evaluation/feedbackalgorithm 220, in conjunction with the controller 218, can be configuredto monitor temperature at the treatment site during therapy andautomatically shut off the energy delivery when the temperature reachesa predetermined maximum (e.g., when applying RF energy) or predeterminedminimum (e.g., when applying cryotherapy). In other embodiments, theevaluation/feedback algorithm 220, in conjunction with the controller218, can be configured to automatically terminate treatment after apredetermined maximum time, a predetermined maximum impedance rise ofthe targeted tissue (i.e., in comparison to a baseline impedancemeasurement), a predetermined maximum impedance of the targeted tissue),and/or other threshold values for biomarkers associated with autonomicfunction. This and other information associated with the operation ofthe system 200 can be communicated to the operator via a display 222(e.g., a monitor or touchscreen) on the console 204 and/or a separatedisplay (not shown) communicatively coupled to the console 204.

In various embodiments, the therapeutic assembly 212 and/or otherportions of the system 200 can be configured to detect variousparameters of the heterogeneous tissue at the target site to determinethe anatomy at the target site (e.g., tissue types, tissue locations,vasculature, bone structures, foramen, sinuses, etc.), locate nervesand/or other structures, and allow for neural mapping. For example, thetherapeutic assembly 212 can be configured to detect impedance,dielectric properties, temperature, and/or other properties thatindicate the presence of neural fibers in the target region. As shown inFIG. 2, the console 204 can include a nerve monitoring assembly 221(shown schematically) that receives the detected electrical and/orthermal measurements of tissue at the target site taken by thetherapeutic assembly 212, and process this information to identify thepresence of nerves, the location of nerves, and/or neural activity atthe target site. This information can then be communicated to theoperator via a high resolution spatial grid (e.g., on the display 222)and/or other type of display. The nerve monitoring assembly 221 can beoperably coupled to the energy delivery element 214 and/or otherfeatures of the therapeutic assembly 212 via signal wires (e.g., copperwires) that extend through the cable 206 and through the length of theshaft 208. In other embodiments, the therapeutic assembly 212 can becommunicatively coupled to the nerve monitoring assembly 221 using othersuitable communication means.

The nerve monitoring assembly 221 can determine neural locations andactivity before therapeutic neuromodulation to determine precisetreatment regions corresponding to the positions of the desired nerves,during treatment to determine the effect of the therapeuticneuromodulation, and/or after treatment to evaluate whether thetherapeutic neuromodulation treated the target nerves to a desireddegree. This information can be used to make various determinationsrelated to the nerves proximate to the target site, such as whether thetarget site is suitable for neuromodulation. In addition, the nervemonitoring assembly 221 can also compare the detected neural locationsand/or activity before and after therapeutic neuromodulation, andcompare the change in neural activity to a predetermined threshold toassess whether the application of therapeutic neuromodulation waseffective across the treatment site. For example, the nerve monitoringassembly 221 can determine electroneurogram (ENG) signals based onrecordings of electrical activity of neurons taken by the therapeuticassembly 212 before and after therapeutic neuromodulation. Statisticallymeaningful (e.g., measurable or noticeable) decreases in the ENGsignal(s) taken after neuromodulation can serve as an indicator that thenerves were sufficiently ablated.

The system 200 can further include a channel 224 extending along atleast a portion of the shaft 208 and a port 226 at the distal portion208 b of the shaft in communication with the port 226. In certainembodiments, the channel 224 is a fluid pathway to deliver a fluid tothe distal portion 208 b of the shaft 208 via the port 226. For example,the channel 224 can deliver saline solution or other fluids to rinse theintraluminal nasal pathway during delivery of the therapeutic assembly212, flush the target site before applying therapeutic neuromodulationto the target site, and/or deliver fluid to the target site duringenergy delivery to reduce heating or cooling of the tissue adjacent tothe energy delivery element 214. In other embodiments, the channel 224allows for drug delivery to the treatment site. For example, a needle(not shown) can project through the port 226 to inject or otherwisedeliver a nerve block, a local anesthetic, and/or other pharmacologicalagent to tissue at the target site.

The therapeutic neuromodulation device 202 provides access to targetsites deep within the nasal region, such as at the immediate entrance ofparasympathetic fibers into the nasal cavity to therapeutically modulateautonomic activity within the nasal cavity. In certain embodiments, forexample, the therapeutic neuromodulation device 202 can position thetherapeutic assembly 212 inferior to the SPF at the site of accessforamen and/or microforamina (e.g., as shown in FIGS. 1B and 1C). Bymanipulating the proximal portion 208 a of the shaft 208 from outsidethe entrance of the nose, a clinician may advance the shaft 208 throughthe tortuous intraluminal path through the nasal cavity and remotelymanipulate the distal portion 208 b of the shaft 208 via the handle 210to position the therapeutic assembly 212 at the target site. In certainembodiments, the shaft 208 can be a steerable device (e.g., a steerablecatheter) with a small bend radius (e.g., a 5 mm bend radius, a 4 mmbend radius, a 3 mm bend radius or less) that allows the clinician tonavigate through the tortuous nasal anatomy. The steerable shaft canfurther be configured to articulate in at least two differentdirections. For example, the steerable shaft 208 can include dual pullwire rings that allow a clinician to form the distal portion 208 b ofthe shaft 208 into an “S”-shape to correspond to the anatomy of thenasal region. In other embodiments, the articulating shaft 208 can bemade from a substantially rigid material (e.g., a metal material) andinclude rigid links at the distal portion 208 b of the shaft 208 thatresist deflection, yet allow for a small bend radius (e.g., a 5 mm bendradius, a 4 mm bend radius, a 3 mm bend radius or less). In furtherembodiments, the steerable shaft 208 may be a laser-cut tube made from ametal and/or other suitable material. The laser-cut tube can include oneor more pull wires operated by the clinician to allow the clinician todeflect the distal portion 208 b of the shaft 208 to navigate thetortuous nasal anatomy to the target site.

In various embodiments, the distal portion 208 b of the shaft 208 isguided into position at the target site via a guidewire (not shown)using an over-the-wire (OTW) or a rapid exchange (RX) technique. Forexample, the distal end of the therapeutic assembly 212 can include achannel for engaging the guidewire. Intraluminal delivery of thetherapeutic assembly 212 can include inserting the guide wire into anorifice in communication with the nasal cavity (e.g., the nasal passageor mouth), and moving the shaft 208 and/or the therapeutic assembly 212along the guide wire until the therapeutic assembly 212 reaches a targetsite (e.g., inferior to the SPF).

In further embodiments, the therapeutic neuromodulation device 202 canbe configured for delivery via a guide catheter or introducer sheath(not shown) with or without using a guide wire. The introducer sheathcan first be inserted intraluminally to the target site in the nasalregion, and the distal portion 208 b of the shaft 208 can then beinserted through the introducer sheath. At the target site, thetherapeutic assembly 212 can be deployed through a distal end opening ofthe introducer sheath or a side port of the introducer sheath. Incertain embodiments, the introducer sheath can include a straightportion and a pre-shaped portion with a fixed curve (e.g., a 5 mm curve,a 4 mm curve, a 3 mm curve, etc.) that can be deployed intraluminally toaccess the target site. In this embodiment, the introducer sheath mayhave a side port proximal to or along the pre-shaped curved portionthrough which the therapeutic assembly 212 can be deployed. In otherembodiments, the introducer sheath may be made from a rigid material,such as a metal material coated with an insulative or dielectricmaterial. In this embodiment, the introducer sheath may be substantiallystraight and used to deliver the therapeutic assembly 212 to the targetsite via a substantially straight pathway, such as through the middlemeatus MM (FIG. 1A).

Image guidance may be used to aid the clinician's positioning andmanipulation of the distal portion 208 b of the shaft 208 and thetherapeutic assembly 212. For example, as described in further detailbelow with respect to FIGS. 3A-3E, an endoscope (not shown) can bepositioned to visualize the target site, the positioning of thetherapeutic assembly 212 at the target site, and/or the therapeuticassembly 212 during therapeutic neuromodulation. In certain embodiments,the distal portion 208 b of the shaft 208 is delivered via a workingchannel extending through an endoscope, and therefore the endoscope canprovide direct in-line visualization of the target site and thetherapeutic assembly 212. In other embodiments, an endoscope isincorporated with the therapeutic assembly 212 and/or the distal portion208 b of the shaft 208 to provide in-line visualization of the assembly212 and/or the surrounding nasal anatomy. In still further embodiments,image guidance can be provided with various other guidance modalities,such as image filtering in the infrared (IR) spectrum to visualize thevasculature and/or other anatomical structures, computed tomography(CT), fluoroscopy, ultrasound, optical coherence tomography (OCT),and/or combinations thereof. Further, in some embodiments, imageguidance components may be integrated with the therapeuticneuromodulation device 202 to provide image guidance during positioningof the therapeutic assembly 212.

Once positioned at the target site, the therapeutic modulation may beapplied via the energy delivery element 214 and/or other features of thetherapeutic assembly 212 to precise, localized regions of tissue toinduce one or more desired therapeutic neuromodulating effects todisrupt parasympathetic motor sensory function. The therapeutic assembly212 can selectively target postganglionic parasympathetic fibers thatinnervate the nasal mucosa at a target or treatment site proximate to orat their entrance into the nasal region. For example, the therapeuticassembly 212 can be positioned to apply therapeutic neuromodulation atleast proximate to the SPF (FIG. 1A) to therapeutically modulate nervesentering the nasal region via the SPF. The therapeutic assembly 212 canalso be positioned to inferior to the SPF to apply therapeuticneuromodulation energy across accessory foramen and microforamina (e.g.,in the palatine bone) through which smaller medial and lateral branchesof the posterior superior lateral nasal nerve enter the nasal region.The purposeful application of the energy at the target site may achievetherapeutic neuromodulation along all or at least a portion of posteriornasal neural fibers entering the nasal region. The therapeuticneuromodulating effects are generally a function of, at least in part,power, time, and contact between the energy delivery elements and theadjacent tissue. For example, in certain embodiments therapeuticneuromodulation of autonomic neural fibers are produced by applying RFenergy at a power of about 2-20 W (e.g., 5 W, 7 W, 10 W, etc.) for atime period of about 1-20 sections (e.g., 5-10 seconds, 8-10 seconds,10-12 seconds, etc.). The therapeutic neuromodulating effects mayinclude partial or complete denervation via thermal ablation and/ornon-ablative thermal alteration or damage (e.g., via sustained heatingand/or resistive heating). Desired thermal heating effects may includeraising the temperature of target neural fibers above a desiredthreshold to achieve non-ablative thermal alteration, or above a highertemperature to achieve ablative thermal alteration. For example, thetarget temperature may be above body temperature (e.g., approximately37° C.) but less than about 90° C. (e.g., 70-75° C.) for non-ablativethermal alteration, or the target temperature may be about 100° C. orhigher (e.g., 110° C., 120° C., etc.) for the ablative thermalalteration. Desired non-thermal neuromodulation effects may includealtering the electrical signals transmitted in a nerve.

Hypothermic effects may also provide neuromodulation. As described infurther detail below, for example, a cryotherapeutic applicator may beused to cool tissue at a target site to providetherapeutically-effective direct cell injury (e.g., necrosis), vascularinjury (e.g., starving the cell from nutrients by damaging supplyingblood vessels), and sublethal hypothermia with subsequent apoptosis.Exposure to cryotherapeutic cooling can cause acute cell death (e.g.,immediately after exposure) and/or delayed cell death (e.g., duringtissue thawing and subsequent hyperperfusion). Embodiments of thepresent technology can include cooling a structure positioned at or neartissue such that the tissue is effectively cooled to a depth where thetargeted postganglionic parasympathetic nerves reside. For example, thecooling structure is cooled to the extent that it causes therapeuticallyeffective, cryogenic posterior nasal nerve modulation.

In certain embodiments, the system 200 can determine the locations ofthe nerves, accessory foramen, and/or microforamina before therapy suchthat the therapeutic neuromodulation can be applied to precise regionsincluding parasympathetic neural fibers. For example, the system 200 mayidentify a target site that has a length and/or width of about 3 mminferior to the SPF, and the therapeutic assembly 212 can applytherapeutic neuromodulation to the identified target site via one ormore applications of therapeutic neuromodulation. In other embodiments,the target site may be smaller or larger (e.g., a 3 cm-long targetregion) based on the detected locations of neural fibers and foramena.This neural and anatomical mapping allows the system 200 to accuratelydetect and therapeutically modulate the postganglionic parasympatheticneural fibers that innervate the mucosa at the numerous neural entrancepoints into the nasal cavity. Further, because there are not any clearanatomical markers denoting the location of the SPF, accessory foramen,and microforamina, the neural mapping allows the operator to identifyand therapeutically modulate nerves that would otherwise beunidentifiable without intricate dissection of the mucosa. In addition,anatomical mapping can also allow the operator to identify certainstructures that the operator may wish to avoid during therapeutic neuralmodulation (e.g., certain arteries).

Sufficiently modulating at least a portion of the parasympathetic nervesis expected to slow or potentially block conduction of autonomic neuralsignals to the nasal mucosa to produce a prolonged or permanentreduction in nasal parasympathetic activity. This is expected to reduceor eliminate activation or hyperactivation of the submucosal glands andvenous engorgement and, thereby, reduce or eliminate the symptoms ofrhinosinusitis. Further, because the system 200 applies therapeuticneuromodulation to the multitude of branches of the posterior nasalnerves rather than a single large branch of the posterior nasal nervebranch entering the nasal cavity at the SPF, the system 200 provides amore complete disruption of the parasympathetic neural pathway thataffects the nasal mucosa and results in rhinosinusitis. Accordingly, thesystem 200 is expected to have enhanced therapeutic effects for thetreatment of rhinosinusitis and reduced re-innervation of the treatedmucosa.

In other embodiments, the system 200 can be configured totherapeutically modulate nerves and/or other structures to treatdifferent indications. As discussed in further detail below, forexample, the system 200 can be used to locate and/or therapeuticallymodulate nerves that innervate the para-nasal sinuses to treat chronicsinusitis. In further embodiments, the system 200 and the devicesdisclosed herein can be configured therapeutically modulate thevasculature within the nasal anatomy to treat other indications, such asepistaxis (i.e., excessive bleeding from the nose). For example, thesystem 200 and the therapeutic neuromodulation devices described hereincan be used to apply therapeutically effective energy to arteries (e.g.,the sphenopalatine artery and its branches) as they enter the nasalcavity (e.g., via the SPF, accessory foramen, etc.) to partially orcompletely coagulate or ligate the arteries. In other embodiments, thesystem 200 can be configured to partially or completely coagulate orligate veins and/or other vessels. For such embodiments in which thetherapeutic assembly 212 ligates or coagulates the vasculature, thesystem 200 would be modified to deliver energy at significantly higherpower (e.g., about 100 W) and/or longer times (e.g., 1 minute or longer)than would be required for therapeutic neuromodulation. In variousembodiments, the system 100 could apply the anatomical mappingtechniques disclosed herein to locate or detect the targeted vasculatureand surrounding anatomy before, during, and/or after treatment.

FIGS. 3A-3E are partial cut-away side views illustrating variousapproaches for delivering a distal portion of the therapeuticneuromodulation device 202 of FIG. 2 to a target site within a nasalregion in accordance with embodiments of the present technology. Asshown in FIG. 3A, in various embodiments the distal portion 208 b of theshaft 208 extends into the nasal passage NP, through the inferior meatusIM between the inferior turbinate IT and the nasal sill NS, and aroundthe posterior portion of the inferior turbinate IT where the therapeuticassembly 212 is deployed at a treatment site. As shown in FIG. 3A, thetreatment site can be located proximate to the access point or points ofpostganglionic parasympathetic nerves (e.g., branches of the posteriornasal nerve and/or other parasympathetic neural fibers that innervatethe nasal mucosa) into the nasal cavity. In other embodiments, thetarget site can be elsewhere within the nasal cavity depending on thelocation of the target nerves. An endoscope 330 and/or othervisualization device is delivered proximate to the target site byextending through the nasal passage NP and through the middle meatus MMbetween the inferior and middle turbinates IT and MT. From thevisualization location within the middle meatus MM, the endoscope 330can be used to visualize the treatment site, surrounding regions of thenasal anatomy, and the therapeutic assembly 212.

As further shown in FIG. 3A, the shaft 208 of the therapeuticneuromodulation device 202 can include a positioning member 332positioned proximal to the therapeutic assembly 212 and the target site.In the illustrated embodiment, the positioning member 332 is a balloonthat is expanded in an opening (e.g., in one of the meatuses) againstopposing structures (e.g., between the turbinates) to consistently holdthe distal portion 208 b of the shaft 208 in a desired position relativeto the target site and provide stability for deployment of thetherapeutic assembly 212. In other embodiments, the positioning member332 may include other expandable structures (e.g., a mesh baskets) oranchor features that can be deployed to maintain a desired position ofthe shaft 208 within the nasal cavity. In further embodiments, thepositioning member 332 can be positioned distal to the therapeuticassembly 212 and expanded in a region distal to the therapeutic assembly212 and the treatment site. In still further embodiments, thepositioning member 332 is positioned on an introducer sheath (not shown)through which the shaft 208 and/or other devices (e.g., a fluid line fordelivery of saline or local anesthetics, an endoscope, a sensor, etc.)can pass. The positioning member 332 can be positioned proximal to thetarget site (e.g., similar to the position shown in FIG. 3A) or distalto the treatment site. When positioned distally, the introducer sheathcan include a side exit port through which the therapeutic assembly 212and other features can be deployed at the target site. When thepositioning member 332 is positioned on the introducer sheath, thepositioning member 332 can provide stability for delivery and deploymentof the distal portion 208 b of the shaft 208 and the therapeuticassembly 212. The positioning member 332 can be incorporated on theshaft 208, an associated introducer sheath, and/or other deliverfeatures of the system 200 (FIG. 2) when the therapeutic assembly 212 isdelivered through different intraluminal passageways.

FIG. 3B illustrates a differ embodiment in which the distal portion 208b of the shaft 208 extends into the nasal passage NP, through the middlemeatus MM between the inferior turbinate IT and the middle turbinate,and in posterior direction where the therapeutic assembly 212 isdeployed at a treatment site. In this embodiment, the endoscope 330and/or other visualization device is delivered alongside the shaft 208through the same intraluminal pathway as the therapeutic assembly 212.The pathway through the middle meatus MM may provide for generallystraight access to the target site depending on the specific region ofinterest and anatomical variations of the patient. Accordingly, anapproach through the middle meatus MM may require less steering and/orarticulation of the shaft 208 and the endoscope 330. Further, becausethe distal portion 208 b of the shaft 208 and the endoscope 330 travelalong the same delivery path, the endoscope can provide in-line orside-by-side visualization of the therapeutic assembly 212.

Similar to the embodiment shown in FIG. 3B, FIG. 3C illustrates anotherintraluminal pathway in which the distal portion 208 b of the shaft 208and the endoscope 330 travel next to each other such that the endoscope330 can provide in-line or side-by-side visualization of the distalportion 208 b of the shaft 208, the therapeutic assembly 212, and/or thenasal anatomy. In the embodiment shown in FIG. 3C, however, theintraluminal pathway extends through the inferior meatus IM to aposterior treatment site.

As shown in FIG. 3D, in other embodiments the distal portion 208 b ofthe shaft 208 extends to the treatment site via the middle meatus MM,and the endoscope 330 extends through the inferior meatus IM to aposition proximate to the target site. In this embodiment, the endoscope330 may have an articulating, steerable, or curved distal end thatdirects the endoscope 330 superiorly to visualize the nasal anatomy andthe therapeutic assembly 332 at the target site. For example, the distalend portion of the endoscope 330 can be configured to bend at least 30°to visualize the treatment site.

As shown in FIG. 3E, in further embodiments the distal portion 208 b ofthe shaft 208 can be delivered to the treatment site via the mouth. Inthis embodiment, therapeutic neuromodulation can be applied at atreatment site posterior to the nasal cavity (e.g., posterior to theSPF). The endoscope 330 (not shown) can extend into the nasal passageNP, through the middle meatus MM or the inferior meatus IM to a positionproximate to the treatment site. Alternatively, the endoscope 330 (notshown) can travel along the same pathway as the shaft 208.

FIG. 4 is an isometric view of a distal portion of a therapeuticneuromodulation device 402 configured in accordance with an embodimentof the present technology. The therapeutic neuromodulation device 402can be used in conjunction with the system 200 described above withrespect to FIGS. 2-3E. As shown in FIG. 4, the therapeuticneuromodulation device 402 can include a shaft 408 having a proximalportion (not shown) and a distal portion 408 b, and a therapeuticassembly 412 at the distal portion 408 b of the shaft 408. Thetherapeutic assembly 412 is transformable between a low-profile deliverystate to facilitate intraluminal delivery of the therapeutic assembly412 to a treatment site within the nasal region and an expanded state(shown in FIG. 4). The therapeutic assembly 412 includes a plurality ofstruts 440 that are spaced apart from each other to form a frame orbasket 442 when the therapeutic assembly 412 is in the expanded state.The struts 440 can carry one or more energy delivery elements, such as aplurality of electrodes 444. In the expanded state, the struts 440 canposition at least two of the electrodes 444 against tissue at a targetsite within the nasal region (e.g., proximate to the palatine boneinferior to the SPF). The electrodes 444 can apply bipolar ormulti-polar radiofrequency (RF) energy to the target site totherapeutically modulate postganglionic parasympathetic nerves thatinnervate the nasal mucosa proximate to the target site. In variousembodiments, the electrodes 444 can be configured to apply pulsed RFenergy with a desired duty cycle (e.g., 1 second on/0.5 seconds off) toregulate the temperature increase in the target tissue.

In the embodiment illustrated in FIG. 4, the basket 442 includes eightbranches 446 spaced radially apart from each other to form at least agenerally spherical structure, and each of the branches 446 includes twostruts 440 positioned adjacent to each other. In other embodiments,however, the basket 442 can include fewer than eight branches 446 (e.g.,two, three, four, five, six, or seven branches) or more than eightbranches 446. In further embodiments, each branch 446 of the basket 442can include a single strut 440, more than two struts 440, and/or thenumber of struts 440 per branch can vary. In still further embodiments,the branches 446 and struts 440 can form baskets or frames having othersuitable shapes for placing the electrodes 444 in contact with tissue atthe target site. For example, when in the expanded state, the struts 440can form an ovoid shape, a hemispherical shape, a cylindrical structure,a pyramid structure, and/or other suitable shapes.

As shown in FIG. 4, the therapeutic assembly 412 can further include aninternal or interior support member 448 that extends distally from thedistal portion 408 b of the shaft 408. A distal end portion 450 of thesupport member 448 can support the distal end portions of the struts 440to form the desired basket shape. For example, as shown in FIG. 4, thestruts 440 can extend distally from the distal portion 408 b of theshaft 408 and the distal end portions of the struts 440 can attach tothe distal end portion 450 of the support member 448. In certainembodiments, the support member 448 can include an internal channel (notshown) through which electrical connectors (e.g., wires) coupled to theelectrodes 444 and/or other electrical features of the therapeuticelement 412 can run. In various embodiments, the internal support member448 can also carry an electrode (not shown) at the distal end portion450 and/or along the length of the support member 448.

The basket 442 can transform from the low-profile delivery state to theexpanded state (FIG. 4) by manipulating a handle (e.g., the handle 210of FIG. 2) and/or other feature at the proximal portion of the shaft 408and operably coupled to the basket 442. For example, to move the basket442 from the expanded state to the delivery state, an operator can pushthe support member 448 distally to bring the struts 440 inward towardthe support member 448. An introducer or guide sheath (not shown) can bepositioned over the low-profile therapeutic assembly 412 to facilitateintraluminal delivery or removal of the therapeutic assembly 412 from orto the target site. In other embodiments, the therapeutic assembly 412is transformed between the delivery state and the expanded state usingother suitable means.

The individual struts 440 can be made from a resilient material, such asa shape-memory material (e.g., Nitinol) that allows the struts 440 toself-expand into the desired shape of the basket 442 when in theexpanded state. In other embodiments, the struts 440 can be made fromother suitable materials and/or the therapeutic assembly 412 can bemechanically expanded via a balloon or by proximal movement of thesupport member 448. The basket 442 and the associated struts 440 canhave sufficient rigidity to support the electrodes 444 and position orpress the electrodes 444 against tissue at the target site. In addition,the expanded basket 442 can press against surrounding anatomicalstructures proximate to the target site (e.g., the turbinates, thepalatine bone, etc.) and the individual struts 440 can at leastpartially conform to the shape of the adjacent anatomical structures toanchor the therapeutic element 412 at the treatment site during energydelivery. In addition, the expansion and conformability of the struts440 can facilitate placing the electrodes 444 in contact with thesurrounding tissue at the target site.

At least one electrode 444 is disposed on individual struts 440. In theillustrated embodiment, two electrodes 444 are positioned along thelength of each strut 440. In other embodiments, the number of electrodes444 on individual struts 440 be only one, more than two, zero, and/orthe number of electrodes 444 on the different struts 440 can vary. Theelectrodes 444 can be made from platinum, iridium, gold, silver,stainless steel, platinum-iridium, cobalt chromium, iridium oxide,polyethylenedioxythiophene (“PEDOT”), titanium, titanium nitride,carbon, carbon nanotubes, platinum grey, Drawn Filled Tubing (“DFT”)with a silver core made by Fort Wayne Metals of Fort Wayne, Ind., and/orother suitable materials for delivery RF energy to target tissue.

In certain embodiments, each electrode 444 can be operated independentlyof the other electrodes 444. For example, each electrode can beindividually activated and the polarity and amplitude of each electrodecan be selected by an operator or a control algorithm (e.g., executed bythe controller 218 of FIG. 2). Various embodiments of such independentlycontrolled electrodes 444 are described in further detail below withreference to FIGS. 5A-5G. The selective independent control of theelectrodes 444 allows the therapeutic assembly 412 to deliver RF energyto highly customized regions. For example, a select portion of theelectrodes 444 can be activated to target neural fibers in a specificregion while the other electrodes 444 remain inactive. In certainembodiments, for example, electrodes 444 may be activated across theportion of the basket 442 that is adjacent to tissue at the target site,and the electrodes 444 that are not proximate to the target tissue canremain inactive to avoid applying energy to non-target tissue. Suchconfigurations facilitate selective therapeutic modulation of nerves onthe lateral nasal wall within one nostril without applying energy tostructures in other portions of the nasal cavity.

The electrodes 444 can be electrically coupled to an RF generator (e.g.,the generator 216 of FIG. 2) via wires (not shown) that extend from theelectrodes 444, through the shaft 408, and to the RF generator. Wheneach of the electrodes 444 is independently controlled, each electrode444 couples to a corresponding wire that extends through the shaft 408.In other embodiments, multiple electrodes 444 can be controlled togetherand, therefore, multiple electrodes 444 can be electrically coupled tothe same wire extending through the shaft 408. The RF generator and/orcomponents operably coupled (e.g., a control module) thereto can includecustom algorithms to control the activation of the electrodes 444. Forexample, the RF generator can deliver RF power at about 200-300 W to theelectrodes 444, and do so while activating the electrodes 444 in apredetermined pattern selected based on the position of the therapeuticelement 412 relative to the treatment site and/or the identifiedlocations of the target nerves. In other embodiments, the RF generatordelivers power at lower levels (e.g., less than 15 W, 15-50 W, 50-150 W,etc.) and/or higher power levels.

As shown in FIG. 4, the therapeutic assembly 412 can further include oneor more temperature sensors 452 disposed on the struts 440 and/or otherportions of the therapeutic assembly 412 and configured to detect thetemperature adjacent to the temperature sensor 452. The temperaturesensors 452 can be electrically coupled to a console (e.g., the console204 of FIG. 2) via wires (not shown) that extend through the shaft 408.In various embodiments, the temperature sensors 452 can be positionedproximate to the electrodes 444 to detect the temperature at theinterface between tissue at the target site and the electrodes 444. Inother embodiments, the temperature sensors 452 can penetrate the tissueat the target site (e.g., a penetrating thermocouple) to detect thetemperature at a depth within the tissue. The temperature measurementscan provide the operator or the system with feedback regarding theeffect of the therapeutic neuromodulation on the tissue. For example, incertain embodiments the operator may wish to prevent or reduce damage tothe tissue at the treatment site (e.g., the nasal mucosa), and thereforethe temperature sensors 452 can be used to determine if the tissuetemperature reaches a predetermined threshold for irreversible tissuedamage. Once the threshold is reached, the application of therapeuticneuromodulation energy can be terminated to allow the tissue to remainintact. In certain embodiments, the energy delivery can automaticallyterminate based on an evaluation/feedback algorithm (e.g., theevaluation/feedback algorithm 220 of FIG. 2) stored on a console (e.g.,the console 204 of FIG. 2) operably coupled to the temperature sensors452.

FIGS. 5A-5G are isometric views of examples of electrode configurationsof therapeutic neuromodulation devices (identified individually as firstthrough fourth therapeutic neuromodulation devices 502 a-502 d,respectively; referred to collectively as therapeutic neuromodulationdevices 502) for therapeutic neuromodulation in accordance withembodiments of the present technology. The therapeutic neuromodulationdevices 502 of FIGS. 5A-5G can include features generally similar to thefeatures of the therapeutic neuromodulation device 402 of FIG. 4. Forexample, the therapeutic neuromodulation devices 502 include a pluralityof struts 440 that form a basket 442 when in an expanded state, and aplurality of electrodes 444 disposed on one or more of the struts 440.In the illustrated embodiments, the first through third therapeuticneuromodulation device 502 a-c shown in FIGS. 5A-5E include a singlestrut 440 corresponding to each branch 446 of the basket 442, whereasthe fourth therapeutic neuromodulation device 502 d shown in FIGS. 5Fand 5G includes two adjacent struts 440 in each branch 446 of the basket442. In other embodiments, however, the branches 446 of the therapeuticneuromodulation devices 502 may have different quantities of struts 440,and apply RF energy in the same manner as described below with referenceto FIGS. 5A-5G. As shown in FIGS. 5A-5G, the electrodes 444 can beindependently controlled and activated via instructions from acontroller (e.g., the controller 218 of FIG. 2) or a generator (e.g.,the generator 216 of FIG. 2) to apply RF energy across selected regionsor segments of the therapeutic assembly 412.

In the embodiment shown in FIG. 5A, two electrodes 444 of thetherapeutic assembly 412 are activated in the first therapeuticneuromodulation device 502 a. More specifically, a first electrode 444 aon a first strut 440 a is activated at a positive polarity, and a secondelectrode 444 b on a second strut 440 b spaced radially apart from thefirst strut 440 a is activated at a negative polarity. The remainder ofthe electrodes 444 remain inactive. Accordingly, as indicated by thearrows, current can flow from the first electrode 444 a to the secondelectrode 444 b through the target tissue across a circumferential orperipheral segment of the therapeutic assembly 412. This configurationmay be used to therapeutically modulate nerves positioned proximate tothe peripheral segment. In other embodiments, different or additionalelectrodes 444 can be activated to have a selected polarity to applytherapeutic neuromodulation across selected regions of the therapeuticassembly 412 in a predetermined manner.

In the embodiment shown in FIG. 5B, the first therapeuticneuromodulation device 502 a is configured to have three selectivelyactive electrodes 444. A first electrode 444 a on a first strut 440 a isactivated at a positive polarity, and second and third electrodes 444 band 444 c on corresponding second and third struts 440 b and 440 c areactivated at a negative polarity. The remainder of the electrodes 444remain inactive. As indicated by the arrows, current can flow throughthe tissue from the first electrode 444 a to the second and thirdelectrodes 444 b and 444 c across a segment of the therapeutic assembly412, and therefore therapeutically modulate nerves positioned proximateto the peripheral segment. In the illustrated embodiment, the second andthird activated electrodes 444 b and 444 c are positioned on struts 440b, 440 c that are radially spaced apart from but adjacent to the firststrut 440 a carrying the first active electrode 444 a. In otherembodiments, however, electrodes 444 positioned on struts 440 spacedfurther from the first strut 440 a to apply energy across a largerand/or wider segment of the therapeutic assembly 412.

In the embodiment shown in FIG. 5C, all of the electrodes 444 in a firsthemispherical region 501 a of the therapeutic assembly 412 areactivated, while the electrodes 444 of the second hemispherical region501 b are not activated. A first electrode on a first strut 440 a isselectively activated at a positive polarity, and a plurality ofelectrodes 444 (identified individually as second through fifthelectrodes 444 b-444 e, respectively) within the first hemisphericalregion 501 a are selectively activated at a negative polarity such thatRF energy is applied across the first hemispherical region 501 a. Thiselectrode activation configuration may be used to apply RF energy acrossone side of the basket 442 to therapeutically modulate nerves on thelateral nasal wall in one nostril. When the therapeutic assembly 412 ispositioned in the other nostril, a different set of electrodes 444 canbe activated across a hemispherical region of the therapeutic assembly412 based on the orientation of the basket 442 with respect to thelateral nasal wall. Further, because the basket 442 has a generallysymmetrical shape (e.g., circular, oval, etc.) and because theelectrodes 444 can be selectively activated, the orientation of thebasket 442 with respect to the target site on the lateral nasal walldoes not matter. Instead, the operator can deploy the therapeuticassembly 412 at the target site irrespective of orientation, andselectively activate the electrodes 444 in a desired arrangement toapply RF energy across the target site.

In the embodiment shown in FIG. 5D, the second therapeuticneuromodulation device 502 b is configured to selectively control thepolarity of a plurality of the electrodes 444 across at least a portionof the therapeutic assembly 412 to apply RF energy in a sesquipolarfashion (i.e., the sequential or transient bipolar pairing ofelectrodes). In the illustrated embodiment, a first electrode 444 a isbiased at a positive polarity and second through seventh electrodes 444b-444 g are controlled to have negative polarities. The second throughseventh electrodes 444 b-444 g are spaced substantially equal distancesapart from the first electrode 444 a such that the electrodes 444 aredimensionally predisposed to multiplex in sequence. In operation, thefirst through seventh electrodes 444 a-444 g are concurrently activated.However, rather than all of the negative electrodes 444 pairing ormultiplexing with the positive first electrode 444 a simultaneously, thefirst electrode 444 a will pair with the individual negative electrodes444 in a sequential manner based on the path of least resistance. Thispath of least resistance is dictated by the natural anatomy of thetreatment site in contact with the electrodes 444. For example, based onthe anatomy at the target site, the first electrode 444 a may initiallypair with the second electrode 444 b. After this initial pairingpreference has dissipated, a second pairing (e.g., with the thirdelectrode 444 c) will occur based on the path of least resistance. Thefirst electrode 444 a will continue to sequentially pair with theremaining activated negative electrodes in a similar manner until athreshold is reached and the electrodes 444 are in a state ofequilibrium in which there is homogenized current flow between all ofthe electrode pairs. With each sequential pairing, the therapeuticassembly 412 increases the size of the ablation zone (i.e., the regionin which therapeutic neuromodulation energy is applied). As indicated bythe numbers 1-6 in FIG. 5D, this sequential pairing of the electrodes444 may occur in a circular direction (e.g., in a counter clockwise orclockwise direction) based on the impedance changes between theelectrodes 444. In other embodiments, the sequential pairing ofelectrodes 444 may occur in a different pattern based on the anatomicalsurroundings and/or the positioning of the electrodes 444. For example,in the illustrated embodiment, the activated electrodes 444 arepositioned in a quadrant of the therapeutic element 412 with equalradial distances between the individual electrode pairs. In otherembodiments, the activated electrodes 444 can be positioned acrosslarger or smaller regions of the therapeutic element 412 to apply energyacross larger or smaller treatment regions.

The sesquipolar application of RF energy allows the therapeutic assembly412 to intelligently apply RF energy across a target site totherapeutically modulate nerves proximate to the treatment site. Forexample, when in an equidistant radial relationship to each other, thenaturally occurring impedance changes between the electrode pairs causethe therapeutic assembly 412 to radially increase the zone of energyapplication with each pairing. In other embodiments, the electrodes 444can be configured to sequentially pair with each other in a manner suchthat the zone of energy application increases in a transverse and/orlongitudinal manner based on the naturally occurring impedance changesbetween the electrodes 444. Further, due to the sequentialimpedance-based pairing of the electrodes 444, the sesquipolararrangement of the therapeutic assembly 412 can inherently limit theenergy applied to tissue at the target site because once the impedanceexceeds a threshold in one electrode pairing, the next electrode pairingwill occur with a lower impedance. In other embodiments, a controller(e.g., the controller 218 of FIG. 2) can include instructions (e.g.,software) that provides for the sequential pairing of electrodes in aradial, transverse, longitudinal, and/or spiral manner.

In further embodiments, portions of the struts 440 themselves can definethe electrodes 444. In this embodiment, the struts 440 are made from anelectrically conductive material and coated with an insulative material(e.g., poly-xylene polymers, including Paralyene C). Portions of thestruts 440 can remain uncoated to define electrodes 444. The locationsof the uncoated portions of the struts 440 (i.e., the electrodes 444)can be selected to provide a desired neuromodulation pattern. Forexample, the uncoated portions can be spaced equally apart from acentral electrode 444 to allow for sesquipolar RF application. In thisembodiment, the conductive struts 440 serve as the electrical connectorsand, therefore, the therapeutic assembly 412 does not require as manywires as if the electrodes 444 were separate elements positioned on thestruts 440.

In the embodiment shown in FIG. 5E, the third therapeuticneuromodulation device 502 c includes a return electrode 503 at thedistal end portion 450 of the support member 448 and selective polaritycontrol of the individual electrodes 444 on the struts 440 to provideradial multiplexing of the electrodes 444. The return electrode 503 hasa negative polarity, and the other electrodes 444 have a positivepolarity. In the illustrated embodiment, all of the electrodes 444 areactivated, but in other embodiments the electrodes 444 can beselectively activated based on a desired energy application zone. Asindicated by the arrows, this configuration applies RF energy across adistal hemispherical region of the basket 442. In other embodiments, thereturn electrode 503 can be positioned elsewhere on the therapeuticassembly 412, and the electrodes 444, 503 can be used to apply RF energyacross different regions of the basket 442. In further embodiments, thereturn electrode 503 can be activated in conjunction with two or more ofthe electrodes 444 on the struts to apply RF energy in a sesquipolarmanner.

In the embodiment shown in FIG. 5F, the fourth therapeuticneuromodulation device 502 d includes branches 446 having two adjacentstruts 440, and the electrodes 444 on the adjacent struts are spacedapart from each other in a longitudinal direction and selectivelyactivated to apply energy in a radial direction across discrete zones.For example, a first electrode 444 a on a first strut 440 a of a firstbranch 446 a may be selectively activated to have a first polarity and asecond electrode 444 b on the adjacent second strut 440 b of the firstbranch 446 a may be selectively activated to have a second polarityopposite the first polarity. As indicated by the arrows in FIG. 5F, thefirst and second electrodes 444 a and 444 b can then apply bipolar RFenergy in a radial direction within a specific region of the therapeuticassembly 412.

As further shown in FIG. 5F, the individual struts 440 can includemultiple electrodes 444 disposed thereon, and the adjacent strut 440 inthe same branch 446 can have a corresponding quantity of electrodes 444to allow for bipolar coupling of each of the electrode pairs alongdiscrete regions of the branch 446. In certain embodiments, theelectrodes of one strut 440 can all have the same polarity (e.g.,coupled to a first wire; not shown), and the electrodes 444 of theadjacent strut 440 in the same branch 446 can all have the oppositepolarity (e.g., coupled to a second wire; not shown). In otherembodiments, the electrodes 444 on an individual strut 440 can beindependently controlled to have a desired polarity.

In various embodiments, the electrode pairing configurations shown inFIG. 5F can be used to detect impedance across selected regions of thetherapeutic assembly 412 defined by the bipolar electrode pairs. Theimpedance measurements can then be used to identify the presence ofneural fibers in the selected regions. If nerves are detected in one ormore specific regions associated with an electrode pair, the sameelectrode pair can be used to apply RF energy to that region andtherapeutically modulate the nerves in that region.

In the embodiment shown in FIG. 5G, the fourth therapeuticneuromodulation device 502 d is configured to selectively control thepolarity of a plurality of the electrodes 444 across at least a portionof the therapeutic assembly 412 to apply RF energy in a multi-polarmanner in a circular or spiral pattern. As shown in FIG. 5G, electrodes444 of one branch 446 can be activated to have negative polarities andelectrodes 444 of another branch 446 can be activated to have positivepolarities. The arrangement of the electrodes 444 and the variabledistances between the electrodes 444 can differ such that the energyapplication zone has a different shape or pattern. In other embodiments,the positive and negative electrodes 444 are spaced apart from eachother at variable distances. Impedance changes resulting from thesurrounding anatomical structures causes the electrodes to pair witheach other in a sequential manner and, thereby, continuously increasethe zone or region in which energy is applied in a radial direction andin a generally spiral manner.

Energy generally travels deeper into the adjacent target tissue thefurther the positive and negative electrode pairs are spaced apart fromeach other. Thus, the depth of influence of the therapeuticneuromodulation energy is expected to increase as the coupled electrodepairs are spaced further apart from each other on the basket 442. In theembodiment illustrated in FIG. 5G, for example, electrode pairs at thedistal and proximal regions of the basket 442 apply energy to shallowerdepths in the target tissue than the electrode pairs positioned on themedial region of the basket 442. Accordingly, the electrodes pairspositioned closer together can therapeutically modulate nerves atshallower depths than the electrode pairs spaced further apart from eachother. As shown in the illustrated embodiment, some of the electrodes444 and/or entire branches 446 of the basket 442 can remain inactive toachieve the desired depth of energy application and/or neuromodulationpattern.

Selected Embodiments of Neural Detection and Mapping

Various embodiments of the present technology can include features thatmeasure bio-electric, dielectric, and/or other properties ofheterogeneous tissue at target sites within the nasal region todetermine the presence, location, and/or activity of neural fibers and,optionally, map the locations of the detected nerves. The featuresdiscussed below can be incorporated into any of the systems and/ordevices disclosed herein to provide an accurate depiction of nerves atthe target site.

Neural detection can occur (a) before the application of a therapeuticneuromodulation energy to determine the presence or location of nervesat the target site and/or record baseline levels of neural activity; (b)during therapeutic neuromodulation to determine the effect of the energyapplication on the neural fibers at the treatment site; and/or (c) aftertherapeutic neuromodulation to confirm the efficacy of the treatment onthe targeted nerves. Due to the anatomical variations of the number andlocations of the parasympathetic neural fibers that innervate the nasalcavity and the numerous access points (e.g., the SPF, accessory foramen,and microforamina) through which they enter the nasal cavity, suchneural detection and mapping can provide an accurate representation ofthe neural anatomy to adequately treat the parasympathetic nerves, notjust the one or two main branches of the posterior nasal nervestraversing the SPF.

In certain embodiments, the systems disclosed herein can use bioelectricmeasurements, such as impedance, resistance, voltage, current density,and/or other parameters (e.g., temperature) to determine the anatomy, inparticular the neural anatomy, at the target site. The location of theneural anatomy can then be used to determine where the treatment site(s)should be with respect to various anatomical structures fortherapeutically effective neuromodulation of the targetedparasympathetic nasal nerves. For example, the information can be usedto determine the treatment site(s) with respect to the location of theturbinates or meatuses.

The bioelectric properties can be detected via electrodes (e.g., theelectrodes 444 of the therapeutic neuromodulation devices 402-502 d ofFIGS. 4-5G). The electrode pairings on a device (e.g., the therapeuticassemblies 412 described with respect to FIGS. 4-5G) can be selected toobtain the bioelectric data at specific zones or regions and at specificdepths of the targeted regions. FIGS. 6A and 6B, for example, arepartially schematic diagrams illustrating configurations of electrodes644 for nerve detection configured in accordance with embodiments of thepresent technology. As shown in FIG. 6A, the further the electrodes 644are apart from each other, the deeper into the tissue the current flows.Accordingly, electrodes 644 can be selectively activated based on thedepth at which the desired measurements should be taken. As shown inFIG. 6B, the spacing between the electrodes 644 along a plane (e.g., thesurface of the tissue, can affect the region in which the measurementsare taken. Thus, electrodes 644 can be selectively activated to obtaininformation (e.g., impedance) at a desired depth and across a desiredregion. In other embodiments, the bioelectric properties can be detectedusing optical coherent tomography (OCT), ultrasound, and/or othersuitable detection modalities.

The measurement of bioelectric properties can provide informationassociated not only with neural fiber locations, but also theidentification of gross anatomy (e.g., turbinates, meatuses, bone,etc.), which can be used to facilitate system delivery andidentification of the target nerves with respect to the gross anatomy.For example, gross target identification can be determined by evaluatingof the incident electromagnetic field on soft and hard tissues withinthe nasal region, which is in turn dependent upon the local geometry andthe dielectric properties of those features. For example, because of thelayered structure of the anatomy of the nasal cavity (e.g., nasalmucosa, submucosa, periosteum, and bony plates), there are largedistinctions in the relative conductance of the soft and hard tissuesthat can be used to differentiate the “deeper” mucosal tissue on theturbinates from the “shallow” tissue off the turbinates.

In certain embodiments, measurements for neuro-mapping can be obtainedby applying a constant current to electrodes and measuring the voltagedifferences between adjacent pairs of electrodes to produce a spectralprofile or map the tissues at the target site. Impedance data can beobtained while applying high, medium, and/or low frequencies to thetarget tissue. At high frequencies, the current passes directly throughcell membranes, and the resultant measurements are indicative of thetissue and liquids both inside and outside the cells. At lowfrequencies, cell membranes impede current flow to provide differentdefining characteristics of the tissue. Accordingly, bioimpedance can beused to measure targeted shapes or electrical properties of tissueand/or other structures of the nasal cavity. In addition, complex neuralmapping can be performed using frequency difference reconstruction,which requires measurement data (e.g., impedance) at two differentfrequencies.

When detecting neural locations and activity via bioelectric properties,the spatial orientation, direction, and activity of the detected nervebundles can be used to further identify and characterize the nerves. Forexample, the measured bioelectric properties can distinguish betweenterminating axons (i.e., entering a detection region, but not exiting),branching axons (i.e., entering the detection region and increasing innumber upon exiting the detecting region), travelling axons (i.e.,entering and exiting the detection region within no change in geometryor numerical value), and/or other properties of nerves. In addition,axon orientations relative to the electrode array can be identified toindicate whether the neural fibers extend parallel (X direction),perpendicular (Y direction), depth penetrating (Z direction), and/or anyrelative position or angulation to these parameters. This informationcan then be used to selectively treat specific neural fibers. Forexample, selected electrode configurations can be applied to treat aspecific region and/or the therapeutic assembly can be moved ormanipulated to treat the nerves from a different orientation orlocation.

In certain embodiments, temperature measurements can be taken todetermine the effect of therapeutic neuromodulation on nasal tissue.FIG. 7, for example, is a graph illustrating threshold levels ofelectrical conductivity of nasal tissue with respect to temperature. Afirst curve 701 depicts the electrical conductivity (σ) of tissue inresponse to temperature and indicates that a temperature of about 70° C.corresponds to a first threshold of the irreversible change in impedanceof the tissue. A second curve 703 shows that the electrical conductivityof the tissue permanently increases significantly (i.e., impedancedecreases) after the tissue has been exposed to temperatures of 70° C.,as it may during therapeutic neuromodulation. If the therapeuticneuromodulation was stopped when the tissue temperature was detected tobe about 70° C., it is expected that there would be a permanentmeasurable change in the conductivity of the tissue without reaching aphase in which the tissue is structurally changed or damaged (e.g., dueto vaporization, desiccation, etc.). However, if the tissue is exposedto temperatures above a second thermal threshold of about 90° C., thetissue undergoes a high degree of tissue desiccation, and thus asignificant decrease in electrical conductivity (i.e., and a higherlevel of in the electrical impedance). A third curve 705 illustratesthis lower electrical conductivity of the tissue after exposure totemperatures above 90° C. Accordingly, in various embodiments, systemsdisclosed herein can be configured to stop neuromodulation when thetemperature reaches about 70° C. (e.g., 70-80° C.) to avoid structuralchanges or damage to the mucosa, but still providing what is expected tobe therapeutically effective neuromodulation.

Neural detection and mapping can provide a pre-procedural assessment ofthe neural anatomy, a mid-procedure assessment and feedback on temporalchanges in tissue during neuromodulation, and/or a post proceduralassessment of the neural activity as a confirmation of effectiveness. Invarious embodiments, the bioelectric measurements taken pre-, mid-, andpost-procedurally can be taken multiple times during each stage of theprocedure to assess and confirm findings. Pre-procedural assessment canbe used to evaluate the bioelectric properties of the native/host tissueto determine a baseline for subsequent actions and as a reference guideagainst source biological signatures to identify anatomical targets ofinterest (e.g., nerves, microforamina, etc.). This information can bedetermined by placing a multi-electrode array in a known spatialconfiguration to detect and then map electro-anatomical characteristics(e.g., variations in the impedance of different tissue types). Theresultant anatomical mapping can comprise a composition of multiple(high density) activation sequence in multiple planes, relying on thevariations in impedance to identify different tissue types andstructures. During the procedure, the impedance measurements can be usedto confirm that the electrodes maintain good contact with tissue at thetarget site. During and after the procedure, the data can be used todetermine whether the mid- or post-procedural recorded spectra has ashape consistent with the expected tissue types. Post-procedurally, theinformation can be used to determine whether the targeted nerves weretherapeutically treated.

In other embodiments, the action potentials of neural fibers can bedetected via electrodes and or other contacts to dynamically map thelocations and/or activity of nerves in the target region. For example,the recorded action potentials can be used to numerically measure, map,and/or produce images of fast neuronal depolarization to generate anaccurate picture of neural activity. In general, the depolarization ofthe neuronal membrane can cause drops in voltage of about 110 μV, hasabout 2 ms, and have an impedance/resistance from 1000 Ωcm to 25 Ωcm. Infurther embodiments, the metabolic recovery processes associated withaction potential activity (i.e., to restore ionic gradients to normal)can also be detected and used for dynamically mapping nerves at thetarget site. The detection of the bioelectric properties associated withthese features has the advantage that the changes are much larger (e.g.,approximately a thousand times larger) and, therefore, easier tomeasure.

In various embodiments, a nontherapeutic stimulation (e.g., RF energy)can be applied to the tissue at the detection region via two or moreelectrodes of an electrode array to enhance the recording of actionpotentials. The stimulating energy application can temporarily activatethe neural fibers and the resultant action potential can be recorded.For example, two or more electrodes of a therapeutic assembly candeliver a stimulating pulse of energy, and two or more other electrodescan be configured to detect the resultant action potential. Thestimulating energy pulses are expected to enhance the action potentialsignal, making it easier to record.

Selected Embodiments of Therapeutic Neuromodulation Devices

FIGS. 8 and 9 are isometric views of a distal portion of a therapeuticneuromodulation device 802 (“device 802”) configured in accordance withan embodiment of the present technology. The device 802 can includevarious features generally similar to the features of the therapeuticneuromodulation devices 402 and 502 a-d described above with referenceto FIGS. 4-5G. For example, the device 802 includes a therapeuticassembly 812 at a distal portion 408 b of a shaft 408. The therapeuticassembly 812 includes a plurality of struts 440 that form branches 446and define an expandable frame or basket 442, and one or more electrodes444 disposed on one or more of the struts 440. As shown in FIGS. 8 and9, the device 902 can further include an expandable member 856 (e.g., aballoon) carried by the support member 448 and expandable within thebasket 442. The expandable member 856 can include a plurality ofelectrodes 858 disposed on the outer surface of the expandable member856. The electrodes 858 can be used for detection of bioelectricfeatures (e.g., impedance) to allow for mapping of the neural anatomy atthe target site before, during, and/or after therapeutic neuromodulationvia the other electrodes 444. In other embodiments, the electrodes 858can be configured to apply energy for therapeutic neuromodulation.

As shown in FIGS. 8 and 9, the electrodes 858 can be positioned on theexpandable member 856 in a substantially symmetrical manner and auniform distribution. This provides an expansive array with whichimpedance and/or other properties can be detected across the tissue and,therefore, may provide a more detailed mapping of the tissue and nervesat the treatment site. In other embodiments, the electrodes 858 can beclustered toward the medial portion of the expandable member 856 and/oraround different portions of the expandable member 856. In certainembodiments, the electrodes 858 can be selectively activated at aspecific polarity, and therefore the electrode array can be configuredin a variety of static configurations and a dynamically change sequences(e.g., sesquipolar application of current) that may be advantageous formapping functions.

In operation, the expandable member 856 can be inflated or otherwiseexpanded (FIG. 9) to place at least a portion of the electrodes 858 intocontact with tissue at the target site. The electrodes 858 can measurevarious bioelectric properties of the tissue (e.g., impedance, actionpotentials, etc.) to detect, locate, and/or map the nerves at thetreatment site. In certain embodiments, the electrodes 444 on the struts440 and/or a portion of the electrodes 858 on the expandable member 856can apply a stimulating pulse of RF energy, and the electrodes 858 candetect the resultant neural response. After mapping, the expandablemember 856 can be deflated or collapsed (FIG. 8), and the electrodes 444on the struts 440 can apply therapeutically effective neuromodulationenergy to the target site. For example, the ablation pattern of theelectrodes 444 can be based on the neural locations identified via theinformation detected from the sensing electrodes 858 on the expandablemember 856. In other embodiments, the expandable member 856 may remainexpanded during neuromodulation, and the electrodes 858 can detectneural activity during the neuromodulation procedure or the electrodes858 can themselves be configured to apply neuromodulation energy to thetreatment site. After applying the neuromodulation energy, theelectrodes 858 on the expandable member 856 can again be placed intocontact with tissue at the target site, and used to record bioelectricproperties (e.g., impedance). The detected properties (e.g., impedances)taken before, during, and/or after neuromodulation can be compared toeach other to determine whether the neuromodulation was therapeuticallyeffective. If not, the electrodes 444 can again apply therapeuticneuromodulation energy to the same treatment site, or the configurationof the active electrodes 444 can be changed to apply therapeuticneuromodulation energy in a different pattern or sequence, and/or thetherapeutic assembly 812 can be moved to a different treatment site.

FIG. 10A is an isometric view of a distal portion of a therapeuticneuromodulation device 1002 (“device 1002”) configured in accordancewith another embodiment of the present technology, and FIG. 10B is anisometric view illustrating the therapeutic neuromodulation device 1002of FIG. 10A at a treatment site. The device 1002 can include variousfeatures generally similar to the features of the therapeuticneuromodulation devices 402, 502 a-d, and 802 described above withreference to FIGS. 4-5G, 8 and 9. For example, the device 1002 includesa shaft 1008 and a therapeutic assembly 1012 at a distal portion 1008 bof the shaft 1008. The therapeutic assembly 1012 includes a plurality ofstruts 1040 that form branches 1046 and define an expandable frame orbasket 1042, and one or more electrodes 1044 disposed on one or more ofthe struts 1040. As shown in FIG. 10A, the device 1002 can furtherinclude a secondary or return electrode 1060 disposed along the distalportion of the shaft 1008. In the illustrated embodiment, the returnelectrode 1060 is a ring electrode having a ring-like shape, but inother embodiments the return electrode 1060 may have other shapes orconfigurations.

The return electrode 1060 may be biased at a negative polarity, and atleast a portion of the electrodes 1044 on the struts 1040 and/or onother portions of the therapeutic assembly 1012 may be biased at apositive polarity. As indicated by the arrows in FIG. 10A, bipolar RFenergy can flow across a region spanning from the therapeutic assembly1012 to the return electrode 1060 on this distal portion 1008 b of theshaft 1008. In various embodiments, the RF energy can be applied in asesquipolar manner (i.e., imbalanced bipolar energy).

As shown in FIG. 10B, the therapeutic assembly 1012 can be positionedinferior to the SPF and superior to the inferior turbinate IT and atleast a portion of the microforamina MF and nerves N traversing thepalatine bone. The return electrode 1060 can be positioned inferior tothe inferior turbinate IT and at least a portion of the microforamina MFand nerves N traversing the palatine bone. RF energy can then be appliedacross a wide region spanning from the therapeutic assembly 1012 to thereturn electrode 1060. As shown in FIG. 10B, for example, the device1002 can apply energy across the top and bottom portions of the inferiorturbinate, where a high density of microforamina reside.

FIGS. 11A-11D are isometric views illustrating distal portions oftherapeutic neuromodulation devices 1102 (referred to individually as afirst device 1102 a and a second device 1102 b) configured in accordancewith further embodiments of the present technology. The first device1102 a can include various features generally similar to the features ofthe therapeutic neuromodulation devices 402, 502 a-d, 802 and 1002described above with reference to FIGS. 4-5G and 8-10B. For example, thefirst device 1102 a includes a shaft 1108 and a therapeutic assembly1112 at a distal portion 1108 b of the shaft 1108. The therapeuticassembly 1112 includes a flexible membrane 1162 that carries a pluralityof electrodes 1144 and/or other energy delivery elements arranged in anarray across the flexible membrane 1162.

As shown in FIGS. 11A-11C, the flexible membrane 1162 can be configuredto transform from a low-profile delivery state (FIG. 11A), to anexpanded state (FIG. 11B) via self-expansion or mechanical expansionmeans, and back to the low-profile delivery or retrieval state (FIG.11C) for removal of the device from the nasal cavity. In the expandedstate shown in FIG. 11B, the flexible membrane can conform to theirregular anatomy of the nasal space (e.g., turbinates, sinus, and/orother para-nasal) to enhance the contact area between the flexiblemembrane 1162 (and the electrodes 1144 disposed thereon) with thenon-planar anatomy. The flexible membrane 1162 can be made from aflexible and dynamic material to support the electrodes 1144. Forexample, in certain embodiments the flexible membrane 1162 can comprisepolymer filaments and/or other materials that add support and structureto the flexible membrane 1162. In various embodiments, the flexiblemembrane 1162 can have pre-set geometry to retain a predetermined shape.For example, the flexible membrane 1162 and/or the electrode array onthe flexible membrane 1162 can retain spherical curvature (e.g., asshown in FIG. 11A).

In various embodiments, the shaft 1108 can be movable relative to theflexible membrane 1162 to allow for deployment and recapture of theflexible membrane 1162. For example, the flexible membrane 1162 may becurled or otherwise folded into a circular shape when in the deliverystate (FIG. 11A). To move to the expanded state (FIG. 11B), componentsof the shaft 1108 can be rotated and/or moved axially relative to theflexible membrane 1162 to unwind or otherwise expand the flexiblemembrane 1162 such that the flexible membrane 1162 at least partiallyopens and conforms to the structures of the surrounding anatomy to placethe electrodes 1144 into contact with tissue at the target site. Torecapture the device to the retracted state (FIG. 11C), the shaft 1108can again be moved axially or rotational manner to close wind orotherwise fold the flexible membrane 1162.

As shown in FIGS. 11A-11C, the electrodes 1144 may be interconnectedthrough a plurality of connectors 1164, such as nano-ribbons,nano-wires, direct inking, multidirectional printing/deposition, and/orother suitable electrical connectors. In various embodiments, theinterconnections 1164 between the electrodes 1144 can include periodicundulating conduits or lines having a “U”, “S”, or elliptical shapes.These undulating connectors 1164 may form a multidimensional springwithin the flexible membrane 1162 and/or impose a predetermined shape onthe flexible membrane 1162 that facilitates apposition of the flexiblemembrane 1162 to the tissue at the target site to improve energyconductivity/transference.

The electrodes 1144 may be surface mounted on the flexible membrane 1162or embedded within a multi-layered composite structure of the flexiblemembrane 1162. In various embodiments, the electrodes 1144 may berelatively small in size, having diameters ranging from 50-2,000microns. The electrodes 1144 may be configured to deliver energy in amono-polar, bipolar, or multipolar manner. For example, multipolarelectrodes can be used in a bipolar arrangement and in a quad-polararrangement to facilitate a linear and an angulated (diagonal) energyconnectivity between the electrodes 1144.

The electrodes 1144 can be connected to a connection pad (not shown)housed within the shaft 1108 and/or features connected to proximalportions of the shaft 1108, such as a handle or console. The electrodes1144 can be connected to the connection pad through a conductiveconnector cable (e.g., a metallic cable, a polymeric cable, and/orcombinations thereof).

In certain embodiments, the flexible membrane 1162 may also house afeedback system (not shown) to control the delivery of the RF energy andmaintain predefined treatment parameters. For example, the electroniccircuits of the flexible membrane 1162 may include thermal sensors thatprovide temperature feedback to control energy dissipation and depthpenetration of the RF energy. The features of electronic circuits of theflexible membrane 1162 may also measure resistance and temperature atthe treatment site to determine the effects of the therapeutic energyapplication. This information may be used to regulate energy applicationand avoid collateral damage to host tissue. For example, energy deliveryvia the electrodes 1144 may be automatically terminated if the detectedtemperature and/or resistance reaches a predetermined threshold maximum(e.g., a threshold temperature associated with tissue damage). Energydelivery via the electrodes 1144 may be automatically or manuallyadjusted if the detected temperature and/or resistance is below apredetermined threshold range indicative of parameters associated withtherapeutically effective modulation of the parasympathetic nasalnerves. In other embodiments, the feedback system can be incorporated tocomponents communicatively coupled with the electrodes 1144 and anyadditional sensors on the flexible membrane 1162. For example, thefeedback system can be stored on the console 204 of FIG. 2 and executedby the controller 218 (FIG. 2).

In the embodiment shown in FIG. 11D, the second device 1102 b caninclude various features generally similar to the features of the firstdevice 1102 a described above with reference to FIGS. 11A-11C. Forexample, the device 1102 b of FIG. 11D includes the flexible membrane1162 that carries a plurality of electrodes 1144 and associatedelectrical connectors 1164 disposed on or embedded in the flexiblemembrane 1162. The device 1102 b further includes an expandable frame1166 carrying the flexible membrane 1162. The frame 1166 may have aU-shape and can be made from a shape memory material (e.g., Nitinol). Inother embodiments, the frame may have different shapes and/or be madefrom different materials suitable for supporting the flexible membrane1162.

In operation, the frame 1166 facilitates the deployment of the flexiblemembrane 1162 against the anatomy of the nasal cavity, and providessupport for the flexible membrane 1162 and the associated array ofelectrodes 1144. The U-shaped frame 1166 can enhance the ability of theflexible membrane 1162 to contact the non-planar anatomy at the targetsite. In various embodiments, for example, the frame 1166 may act as acantilever spring to establish a positive directional apposition of themembrane 1162 to the target surface tissue to improve energyconductivity/transference from the electrodes 1144 to the target tissue.

FIG. 12 is a side view of a distal portion of a therapeuticneuromodulation device 1202 (“device 1202”) configured in accordancewith a further embodiment of the present technology. The device 1202includes include various features generally similar to the features ofthe therapeutic neuromodulation devices 402, 502 a-d, 802, 1002 and 1102described above with reference to FIGS. 4-5G and 8-11. For example, thedevice 1202 includes a shaft 1208 and a therapeutic assembly 1212including a plurality of energy delivery elements, such as electrodes1244, at a distal portion 1208 b of the shaft 1208. In the illustratedembodiment, the therapeutic assembly 1212 includes four electrodes 1244are arranged along a spiral/helical section 1268 at the distal portion1208 b of the shaft 1208. In other embodiments, however, the therapeuticassembly 1212 may include one, two, three, or more than four electrodes1244, and/or may include different energy delivery elements. Thetherapeutic assembly 1212 can also include a temperature sensor 1252(e.g., a thermocouple) and/or other type of sensor to detect variousproperties at the treatment site before, during, and/or after applyingtherapeutic neuromodulation energy, and provide feedback that may beused to control the operation of the therapeutic assembly 1212. Suchsensors can be incorporated in any of the other embodiments oftherapeutic assemblies disclosed herein.

During delivery of the therapeutic assembly 1212, the spiral/helicalsection 1168 of the shaft 1208 is positioned in a low-profile deliverystate in which the section 1268 is substantially straitened or flattenedwithin an introducer sheath and/or via mechanical components associatedwith the shaft 1208. At the target site, the operator can transform thespiral/helical section 1268 to an expanded state (shown in FIG. 12) toplace one or more of the electrodes 1244 in contact with the targettissue. One or more of the electrodes 1244 can then be selectivelyactivated to apply RF energy (e.g., monopolar and/or bipolar RF energy)to tissue at a target site in the nasal region to therapeuticallymodulate nerves proximate to the treatment site. In other embodiments,the distal section of the shaft 1208 can have other suitable shapes,sizes, and/or configurations that facilitate placing the electrodes 1244in contact with tissue at the target site. For example, in furtherembodiments, the distal portion 1208 b of the shaft 1208 can have asemi-circular, curved, bent, or straight shape and/or the therapeuticassembly 1212 can include multiple support members configured to carryone or more of the electrodes 1244.

FIG. 13 is a side view of a distal portion of a therapeuticneuromodulation device 1302 (“device 1302”) configured in accordancewith a still further embodiment of the present technology. The device1302 includes include various features generally similar to the featuresof the therapeutic neuromodulation devices 402, 502 a-d, 802, 1002, 1102and 1202 described above with reference to FIGS. 4-5G and 8-12. Forexample, the device 1302 includes a shaft 1308 and a therapeuticassembly 1312 including a plurality of energy delivery elements, such asan array of electrodes 1344, at a distal portion 1308 b of the shaft1308. In the embodiment illustrated in FIG. 13, the therapeutic assembly1312 includes a balloon 1370 that carries the electrodes 1344. A supportmember 1372 can extend through the length of the balloon 1370 to supportthe balloon 1370 and, optionally, include a channel through which aguidewire (not shown) can extend to facilitate delivery of thetherapeutic assembly 1312 to the target site. In other embodiments, thesupport member 1372 may be omitted.

The electrodes 1344 can be made from conductive ink that is printed,sprayed, and/or otherwise disposed on the surface of the balloon 1370.Such conductive ink electrodes facilitates the use of complex electrodeconfigurations. In addition, thermocouples (not shown) can also beincorporated onto the surface of the balloon 1370 using conductive inkand/or other suitable methods. In other embodiments, the electrodes 1344can be made from foil and adhered to the surface of the balloon 1370. Infurther embodiments, the electrodes 1344 can be made from other suitablematerials that may be disposed on the surface of the balloon 1370 and/orembedded within the material of the balloon 1370.

The balloon 1370 can be made from various different materials and havevarious different shapes. As shown in FIG. 13, for example, the balloon1370 can have an ovoid shape when in the expanded state, which isexpected to improve the conformance to anatomical variations at thetarget site within the nasal cavity. In other embodiments, the balloon1370 can have a circular shape, a spherical shape, an irregular shape,and/or other suitable shape for expansion within the nasal anatomy. Theballoon 1370 can be made from a compliant material (e.g., a urethanematerial) that allows the balloon 1370 to conform to anatomicalvariances when expanded within the nasal region. In other embodiments,the balloon may be made from a non-compliant material (e.g.,polyethylene terephthalate, nylon, etc.) that allows the balloon 1370 tohave a defined shape when expanded and facilitates the attachment ofelectrodes 1344 to the balloon surface. In further embodiments, theballoon 1370 may be dip-coated and form a bulbous tip at the distal endof the shaft 1308.

The balloon 1370 may be inflated with a fluid via an opening or port1374 in the support member 1372 and/or an opening in the shaft 1308 influid communication with the interior of the balloon 1370. For example,the support member 1372 and/or the shaft 1308 can include a channelextending along the length of the shaft 1308 and connected to a fluidsupply at the proximal portion of the shaft 1308 such that fluid can bedelivered to the balloon 1370. The balloon 1370 can inflate against thenasal anatomy at the target site to places the electrodes 1344 incontact with tissue at the target site.

At the target site, the electrodes 1344 deliver RF energy to tissue totherapeutically modulate nerves at the treatment site. In certainembodiments, the array of electrodes 1344 can be arranged on the balloon1370 and/or selectively activated to apply transverse bipolar RF energyacross a radial regions of the balloon 1370 (i.e., extending aroundcircumferential portions of the balloon 1370). In other embodiments, thearray of electrodes 1344 can be arranged on the balloon 1370 and/orselectively activated to apply longitudinal bipolar RF energy acrosslongitudinal regions of the balloon 1370 (i.e., extending betweenproximal and distal portions of the balloon 1370).

In various embodiments, the therapeutic assembly 1312 may includefeatures that facilitate with positioning of the balloon 1370 within thenasal anatomy and proper placement of the electrodes 1344 at thetreatment site. As shown in FIG. 13, for example, an endoscope 1371 maybe positioned on the surface of the balloon 1370 to provide direct,in-line visualization of the balloon 1370 and the target site duringplacement at the target site. The therapeutic assembly 1312 can alsoinclude graduated markings 1373 along the support member 1372 and/or thesurface of the balloon 1370 to depict spatial orientation and/or depthpositioning of the therapeutic assembly 1312.

In certain embodiments, the balloon 1370 can be configured to allow fora slow perfusion of fluid through the balloon wall to cool theelectrodes 1344 while energy is applied to the target tissue. Forexample, such a “weeping” balloon 1370 can include laser-driller holesand/or other small openings or pores along at least a portion of theballoon 1370 to allow for the slow perfusion of a fluid (e.g., salinesolution) through the balloon wall. When the balloon perfuses salinesolution, the saline solution is expected to improve the electricalconductivity between the electrodes 1344 and the target tissue and mayenhance the effect of the RF energy on the nerves at the target site. Inother embodiments, a cooled fluid can be circulated through the balloon1470 during activation of the electrodes 1444 to cool the electrodes1444 and the surrounding tissue during energy delivery.

FIG. 14 is a side view of a distal portion of a therapeuticneuromodulation device 1402 (“device 1402”) configured in accordancewith an additional embodiment of the present technology. The device 1402includes include various features generally similar to the features ofthe therapeutic neuromodulation device 1302 described above withreference to FIG. 13. For example, the device 1402 includes a shaft 1408and a therapeutic assembly 1412 at a distal portion 1408 b of the shaft1408. The therapeutic assembly 1412 includes a balloon 1470, a supportmember 1472 supporting the balloon 1470, and a plurality of energydelivery elements, such as an array of electrodes 1444 disposed on theballoon 1470. In the embodiment illustrated in FIG. 14, the electrodes1444 are part of a flex circuit 1476 adhered to the surface of theballoon 1470. The flex circuit 1476 facilitates the creation of complexelectrode arrays that can create highly customizable neuromodulationpatterns. In certain embodiments, for example, the flex circuit 1476 caninclude a conductive return electrode along the surface of the balloon1470 and a plurality of electrodes on a proximal or distal portion ofthe balloon 1470 (e.g., a conical end portion of the balloon 1470). Inaddition, the flex circuit 1476 can incorporate thermocouples and/orthermistors into the circuitry on the surface of the balloon 1470 todetect temperature at the treatment site before, during, and/or afterenergy application.

FIG. 15 is an isometric side view of a distal portion of a therapeuticneuromodulation device 1502 (“device 1502”) configured in accordancewith an additional embodiment of the present technology. The device 1502includes include various features generally similar to the features ofthe therapeutic neuromodulation devices 1302 and 1402 described abovewith reference to FIGS. 13 and 14. For example, the device 1502 includesa shaft 1508 and a therapeutic assembly 1512 at a distal portion 1508 bof the shaft 1508. The therapeutic assembly 1512 includes a plurality ofballoons 1578 positioned around an inner support member 1580, and aplurality of energy delivery elements, such as electrodes 1544 disposedon one or more of the balloons 1578. In certain embodiments, theballoons 1578 are independently inflatable. This allows for asymmetricalor variable inflation of the balloons 1578 and, thereby, enhances theability of the therapeutic assembly 1512 to conform to the irregulargeometry of the nasal region at the target site and facilitatesapposition of the electrodes 1544 against tissue at the target site.

In the illustrated embodiment, four independently inflated balloons 1578are positioned around the perimeter of the inner support member 1580. Inother embodiments, however, the device 1502 can include less than fourballoons 1578 or more than four balloons 1578 arranged around the innersupport member 1580. In further embodiments, the balloons 1578 can havedifferent sizes and/or shapes, and can be positioned along variousportions of the inner support member 1580. In still further embodiments,the balloons 1578 re configured as struts that are attached at endportions to the inner support member 1580 and extend outwardly away fromthe inner support member 1580 when inflated (e.g., in a similar manneras the struts 440 of the therapeutic neuromodulation device 402 of FIG.4).

During energy delivery, the electrodes 1544 can be configured to applybipolar RF energy across the electrodes 1544 on different balloons 1578and/or between electrodes 1544 on the same balloon 1578. In otherembodiments, the electrodes 1544 apply energy in a sesquipolar manner.For example, the inner support member 1580 can include a returnelectrode (not shown), and the electrodes 1544 on two or more of theballoons 1578 may be activated for sesquipolar RF energy delivery.

FIG. 16 is a cross-sectional side view of a distal portion of atherapeutic neuromodulation device 1602 (“device 1602”) configured inaccordance with an additional embodiment of the present technology. Thedevice 1602 includes various features generally similar to the featuresof the therapeutic neuromodulation devices described above. For example,the device 1602 includes a shaft 1608 and a therapeutic assembly 1612 ata distal portion 1608 b of the shaft 1608. In the embodiment illustratedin FIG. 16, the therapeutic assembly 1612 is configured to applycryotherapeutic cooling to therapeutically modulate nerves at the targetsite. As shown in FIG. 16, the cryotherapeutic assembly 1612 can includean expansion chamber 1682 (e.g., a balloon, inflatable body, etc.) influid communication with one or more supply tubes or lumens 1684 viacorresponding orifices 1686 in the supply lumens 1684. The supply lumens1682 can extend along at least a portion of the shaft 1608 and beconfigured to transport a refrigerant in an at least a partially liquidstate to the distal portion 1608 b of the shaft 1608. An exhaust tube orlumen 1689 (e.g., defined by a portion of the shaft 1608) can be placedin fluid communication with the interior of the expansion chamber 1682via an outlet 1688 such that the exhaust lumen 1689 can return therefrigerant to the proximal portion of the shaft 1608. For example, inone embodiment, a vacuum (not shown) at the proximal portion of theshaft 1608 may be used to exhaust the refrigerant from the expansionchamber 1682 via the exhaust lumen 1689. In other embodiments, therefrigerant may be transported to the proximal portion of the shaft 1608using other suitable mechanisms known to those having skill in the art.

During cryotherapy, the orifices 1686 of the supply lumens 1684 canrestrict refrigerant flow to provide a high pressure differentialbetween the supply lumen 1684 and the expansion chamber 1682, therebyfacilitating the expansion of the refrigerant to the gas phase withinthe expansion chamber 1682. The pressure drop as the liquid refrigerantpasses through the orifices 1682 causes the refrigerant to expand to agas and reduces the temperature to a therapeutically effectivetemperature that can modulate neural fibers proximate a treatment sitewithin the nasal cavity. In the illustrated embodiment, the expansionchamber 1682 includes heat transfer portions 1691 that contact and cooltissue at the target site at a rate sufficient to cause cryotherapeuticneuromodulation of postganglionic parasympathetic neural fibers thatinnervate the nasal mucosa. For example, the therapeutic assembly 1602can operate at temperatures of −40° C., −60° C., −80° C., or lower. Inother embodiments, the therapeutic assembly 1602 can operated at highercryotherapeutic temperatures (e.g., 5° C. and −15° C., −20° C., etc.).

The refrigerant used for cryogenic cooling in the device 1602 can be acompressed or condensed gas that is stored in at least a substantiallyliquid phase, such as nitrous oxide (N₂O), carbon dioxide (CO₂),hydrofluorocarbon (e.g., FREON made available by E. I. du Pont deNemours and Company of Wilmington, Del.), and/or other suitable fluidsthat can be stored at a sufficiently high pressure to be in at least asubstantially liquid phase at about ambient temperature. For example,R-410A, a zeotropic, but near-azeotropic mixture of difluoromethane(CH₂F₂; also known as HFC-32 or R-32) and pentafluoroethane (CHF₂CF₃;also known as HFC-125 or R-125), can be in at least a substantiallyliquid phase at about ambient temperature when contained at a pressureof about 1.45 MPa (210 psi). Under proper conditions, these refrigerantscan reach cryotherapeutic temperatures at or near their respectivenormal boiling points (e.g., approximately −88° C. for nitrous oxide) toeffectuate therapeutic neuromodulation.

In other embodiments, the therapeutic assembly 1612 can include acryotherapeutic applicator rather than the expansion chamber 1682 ofFIG. 16. Such a cryotherapeutic applicator can be used for very targetedtreatment of the nerves.

As further shown in FIG. 16, the device 1602 can also include a supportmember 1690 extending through the expansion chamber 1682 and configuredto carry the distal portion of the expansion chamber 1682. The supportmember 1690 can also include a channel extending along its length and anopening 1692 at the distal end portion of the support member 1690 tofacilitate delivery of the therapeutic assembly 1612 to the treatmentsite via a guidewire GW.

FIG. 17 is a cross-sectional side view of a distal portion of atherapeutic neuromodulation device 1702 (“device 1702”) configured inaccordance with an additional embodiment of the present technology. Thedevice 1702 includes various features generally similar to the featuresof the therapeutic neuromodulation devices described above. For example,the device 1702 includes a shaft 1708 and a therapeutic assembly 1712 ata distal portion 1708 b of the shaft 1708. In the embodiment illustratedin FIG. 17, the therapeutic assembly 1712 is configured to apply directconductive heating to thermally therapeutically modulate nerves at thetarget site. As shown in FIG. 17, the therapeutic assembly 1712 caninclude a balloon 1770 in fluid communication with a supply tube orlumen 1794 (e.g., defined by a portion of the shaft 1708) via an outletat a distal portion of the supply lumen 1794. The supply lumen 1794 canextend along at least a portion of the shaft 1708 and be insulated totransport a heated fluid (e.g., heated saline) to the balloon 1770 atthe distal portion 1708 b of the shaft 1708. An exhaust or return tubeor lumen 1796 (e.g., defined by a portion of the shaft 1708) can beplaced in fluid communication with the interior of the balloon 1770 viaan outlet such that the return lumen 1796 can exhaust the fluid to theproximal portion of the shaft 1708 (e.g., using a vacuum at the proximalportion of the shaft 1708).

During thermal therapeutic neural modulation, the supply lumen 1794 cansupply a heated fluid to the balloon 1770, and the exhaust lumen 1796can be used to exhaust the fluid from the balloon 1770 such that theheated fluid circulates through the balloon 1770 (e.g., as indicated bythe arrows). The heated fluid can be heated to a therapeuticallyeffective temperature that causes time-dependent thermal damage (e.g.,determined using the Arrhenius equation) to the target tissue at atreatment site within the nasal cavity and modulates neural fiberswithin or proximate to the heated target tissue. In the illustratedembodiment, for example, the wall of the balloon 1770 and/or portionsthereof can contact and heat tissue at the target site at a rate andtime sufficient to cause thermal damage to the target tissue to providetherapeutic neuromodulation of postganglionic parasympathetic neuralfibers that innervate the nasal mucosa.

As shown in FIG. 17, the device 1702 can also include a support member1790 extending through the balloon 1770 and configured to carry thedistal portion of the balloon 1770. The support member 1790 can alsoinclude a channel extending along its length and an opening 1792 at thedistal end portion of the support member 1790 that can be used tofacilitate delivery of the therapeutic assembly 1712 to the treatmentsite via a guidewire GW.

FIG. 18 is a cross-sectional side view of a distal portion of atherapeutic neuromodulation device 1802 (“device 1802”) configured inaccordance with an additional embodiment of the present technology. Thedevice 1802 includes various features generally similar to the featuresof the therapeutic neuromodulation devices described above. For example,the device 1802 includes a shaft 1808 and a therapeutic assembly 1812 ata distal portion 1808 b of the shaft 1808. The therapeutic assembly 1812can include an inflatable balloon 1870 and a support member 1890extending through the balloon 1870. The support member 1890 may alsoinclude a channel with an opening 1892 that allows for guidewiredelivery of the therapeutic assembly 1812 to the treatment site.

Similar to the therapeutic assembly 1712 of FIG. 17, the therapeuticassembly 1812 can apply therapeutically effective heating to tissue at atarget site to cause time-dependent thermal tissue damage (e.g.,determined using the Arrhenius equation) and modulate neural fiberswithin or proximate to the heated target tissue. In the embodimentillustrated in FIG. 18, however, heating is supplied via a heatingelement 1898 positioned within the balloon 1880 and carried by thesupport member 1890 and/or another feature of the therapeutic assembly1812. The heating element 1898 may be a plate or other structure heatedusing resistive heating (via a generator) and/or other suitable heatingmechanism. In operation, the heat from the heating element 1898 cantransfer from the heating element 1898 to the fluid within the balloon1870, and then through the wall of the balloon 1870 to the adjacenttissue at the treatment site. The fluid heated by the heating element1898 can be heated to a therapeutically effective temperature thatcauses thermal damage to the target tissue at a treatment site withinthe nasal cavity and modulates neural fibers within or proximate to theheated target tissue. In certain embodiments, the balloon 1870 caninclude conductive features (e.g., metallic panels) on its surface toconcentrate the heating effect at targeted regions of the balloon 1870.

In other embodiments, the balloon 1870 can be heated via capacitivecoupling to reach therapeutically effective temperatures that causesthermal damage to the target tissue at a treatment site within the nasalcavity and modulate neural fibers within or proximate to the heatedtarget tissue. For example, the balloon 1870 can be inflated with anisotonic solution, and the balloon 1870 can be ionically agitated at ahigh frequency to allow capacitive energy to discharge across themembrane of the balloon 1870 to the target tissue.

FIG. 19 is a side view of a distal portion of a therapeuticneuromodulation device 1902 (“device 1902”) configured in accordancewith an additional embodiment of the present technology. The device 1902includes various features generally similar to the features of thetherapeutic neuromodulation devices described above. For example, thedevice 1902 includes a shaft 1908 and a therapeutic assembly 1912 at adistal portion 1908 b of the shaft 1908. In the embodiment illustratedin FIG. 19, the therapeutic assembly 1912 is configured to apply plasmaor laser ablation to therapeutically modulate nerves at the target site.As shown in FIG. 19, the therapeutic assembly 1912 can include anablation element 1999 (e.g., an electrode) on a distal end portion ofthe shaft 1908. The ablation element 1999 can apply high energy laserpulses to ionize molecules within the first few portion of the pulse.This process leads to a small bubble or field of plasma (e.g., 100-200μm) that can be used to desiccate or otherwise destroy tissue and nervesat the target site. The ablation element 1999 can operate attemperatures lower than 100° C. and can limit the thermal effects onsurrounding tissue.

In other embodiments, the ablation element 1999 can perform laserablation of nerves at the target site. For example, a nerve tracer(e.g., indocyanine green (ICG)) can be injected at the target site todye nerves at the target site. The ablation element 1999 can be a laserthat is tuned to absorb the spectrum of the nerve tracer and, thereby,ablate the dyed nerves in the target site.

Selected Embodiments of Therapeutic Neuromodulation for the Treatment ofChronic Sinusitis

FIG. 20 is a partial cut-away side view illustrating target sitesproximate to ostia of nasal sinuses for a therapeutic neuromodulationdevice configured in accordance with embodiments of the presenttechnology. Any of the therapeutic modulation devices and systemdescribed above can be used to therapeutically modulate nerves thatinnervate the para-nasal sinuses to treat chronic sinusitis and/orsimilar indications. Referring to FIG. 20, the para-nasal sinusesinclude the frontal sinuses FS, the sphenoidal sinuses SS, the maxillarysinuses (“MS”; not shown), and the ethmoidal sinuses or ethmoidal cells(not shown), which include the posterior ethmoidal cells (“PEC”), themiddle ethmoidal cells (“MEC”), and the anterior ethmoidal cells(“AEC”). Each sinus opens to the nasal cavity at one or more discreteostia. FIG. 20 illustrates the general locations of the ostium of thefrontal sinus, the sphenoidal sinus, the maxillary sinus, and the ostiaof posterior, middle, and anterior ethmoidal cells.

Parasympathetic nerves innervate the mucosa of the sinuses and stimulatethe production of mucus in the sinuses. Hyperactivity of theparasympathetic nerves innervating the sinuses can cause hyperproduction of mucus and the soft tissue engorgement. The inflammation ofthe soft tissue proximate to the sinuses can cause can obstruct theconduit between a sinus and the nasal cavity and block the ostium to thesinus. In addition, the hyperactive mucosa and/or the blockage of theostium can cause the pooling of mucosal secretions within the sinusoccurs due to the lack of drainage from the sinus. This can lead toinfection and, eventually, a chronic sinusitis state.

Therapeutic modulation the parasympathetic nerves that control autonomicfunction of the sinuses is expected to reduce or eliminate thehyperactive mucosal secretions and soft tissue engorgement and, thereby,treat chronic sinusitis or related indications. Any of the therapeuticneuromodulation devices described above can be used to applytherapeutically effective neuromodulation energy at or proximate to theostia of the affected sphenoidal, maxillary, frontal, and/or ethmoidalsinuses to modulate the autonomic function of the sinuses. For example,therapeutic neuromodulation devices can be used to apply RF energy,microwave energy, ultrasound energy, cryotherapeutic cooling,therapeutic heating, plasma ablation, and/or laser ablation to treatmentsites at and around the ostia of the sinuses. Similar to the devicesdescribed above, the therapeutic neuromodulation devices can bedelivered intraluminally via the nasal passage and through the superior,middle, and/or inferior meatuses to access the ostium or ostia of thedesired sinus. In various embodiments, neural mapping techniques similarto those described above with respect to FIGS. 6A-9 can be used tolocate or detect the parasympathetic nerves that innervate the ostiabefore, during, and/or after treatment. The application of therapeuticneuromodulation at the target sites proximate to the sinus ostia candisrupt the parasympathetic signals to the sinus tissues, leading to theopening of the ostia and the ability to drain fluid.

CONCLUSION

This disclosure is not intended to be exhaustive or to limit the presenttechnology to the precise forms disclosed herein. Although specificembodiments are disclosed herein for illustrative purposes, variousequivalent modifications are possible without deviating from the presenttechnology, as those of ordinary skill in the relevant art willrecognize. In some cases, well-known structures and functions have notbeen shown and/or described in detail to avoid unnecessarily obscuringthe description of the embodiments of the present technology. Althoughsteps of methods may be presented herein in a particular order, inalternative embodiments the steps may have another suitable order.Similarly, certain aspects of the present technology disclosed in thecontext of particular embodiments can be combined or eliminated in otherembodiments. Furthermore, while advantages associated with certainembodiments may have been disclosed in the context of those embodiments,other embodiments can also exhibit such advantages, and not allembodiments need necessarily exhibit such advantages or other advantagesdisclosed herein to fall within the scope of the present technology.Accordingly, this disclosure and associated technology can encompassother embodiments not expressly shown and/or described herein.

Throughout this disclosure, the singular terms “a,” “an,” and “the”include plural referents unless the context clearly indicates otherwise.Similarly, unless the word “or” is expressly limited to mean only asingle item exclusive from the other items in reference to a list of twoor more items, then the use of “or” in such a list is to be interpretedas including (a) any single item in the list, (b) all of the items inthe list, or (c) any combination of the items in the list. Additionally,the terms “comprising” and the like are used throughout this disclosureto mean including at least the recited feature(s) such that any greaternumber of the same feature(s) and/or one or more additional types offeatures are not precluded. Directional terms, such as “upper,” “lower,”“front,” “back,” “vertical,” and “horizontal,” may be used herein toexpress and clarify the relationship between various elements. It shouldbe understood that such terms do not denote absolute orientation.Reference herein to “one embodiment,” “an embodiment,” or similarformulations means that a particular feature, structure, operation, orcharacteristic described in connection with the embodiment can beincluded in at least one embodiment of the present technology. Thus, theappearances of such phrases or formulations herein are not necessarilyall referring to the same embodiment. Furthermore, various particularfeatures, structures, operations, or characteristics may be combined inany suitable manner in one or more embodiments.

We claim:
 1. A system for therapeutic neuromodulation in a nasal regionof a human patient, the system comprising: a shaft having a proximalportion and a distal portion; a therapeutic assembly at the distalportion of the shaft, wherein the therapeutic assembly comprises aplurality of struts, at least some of the struts comprising one or moreelectrodes configured to directly contact tissue, wherein the one ormore electrodes are individually activatable; and a controller operablycoupled to the therapeutic assembly, wherein the controller isconfigured to selectively activate the electrodes of the therapeuticassembly by: detecting a target location of postganglionicparasympathetic nerves innervating nasal mucosa and/or submucosa,inferior to a sphenopalatine foramen and/or at microforamina of apalatine bone of the human patient, based on measured bioelectricproperties of a target tissue at a target site, selecting two or moreelectrodes having a spacing therebetween configured to deliverneuromodulation energy at the target location of the postganglionicparasympathetic nerves, activating the two or more electrodes while thetwo or more electrodes are in direct contact with the target tissue todeliver the neuromodulation energy at the target location; andmaintaining electrodes that are not proximate to the target tissue in aninactive state to avoid applying energy to non-target tissue.
 2. Thesystem of claim 1 wherein the therapeutic assembly includes an energydelivery element configured to deliver at least one of ultrasoundenergy, microwave energy, laser energy, or radiofrequency (RF) energy totherapeutically modulate the postganglionic parasympathetic nerves. 3.The system of claim 1 wherein the therapeutic assembly is configured todispense a drug to chemically modulate the postganglionicparasympathetic nerves.
 4. The system of claim 1 wherein the shaftcomprises a drug delivery channel with an outlet at the distal portionof the shaft, and wherein the drug delivery channel is configured todeliver at least one of a local anesthetic or a nerve block to thetarget site.
 5. The system of claim 1 wherein the shaft comprises afluid channel with an outlet at the distal portion of the shaft, andwherein the fluid channel is configured to deliver saline to the targetsite to rinse a treatment area with saline.
 6. The system of claim 1,further comprising an introducer having a rigid metal portion, andwherein the rigid metal portion is sized and shaped to extend through anasal meatus to the target site to deliver the therapeutic assembly tothe target site.
 7. The system of claim 1 wherein the shaft is asteerable catheter shaft and the distal portion of the shaft has a bendradius of 3 mm or less.
 8. The system of claim 1 wherein the distalportion of the shaft comprises an articulating region with rigid linkssized and shaped to have a bend radius of 3 mm or less.
 9. The system ofclaim 1, further comprising an anchor member along the shaft, whereinthe anchor member includes a balloon configured to expand in a lumen ofthe nasal region to hold the distal portion of the shaft in place fordeployment of the therapeutic assembly at the target site.
 10. Thesystem of claim 1 wherein the therapeutic assembly comprises a pluralityof sensing electrodes configured to detect neural activity at least oneof before therapeutic modulation, during therapeutic modulation, orafter therapeutic neuromodulation.
 11. The system of claim 1 wherein theplurality of struts form a basket transformable between a low-profiledelivery state and an expanded state, wherein the plurality of strutsare spaced radially apart from each other when the basket is in theexpanded state, wherein the plurality of struts are configured toposition at least two of the electrodes at the target site when thebasket is in the expanded state, and wherein the electrodes areconfigured to apply radiofrequency (RF) energy to the target site. 12.The system of claim 1 wherein the therapeutic assembly comprises: aflexible membrane transformable between a low-profile delivery state andan expanded state; and a plurality of electrodes disposed on theflexible membrane, wherein the electrodes are configured to applyradiofrequency (RF) energy to the target site to therapeuticallymodulate parasympathetic nerves proximate to the target site.
 13. Thesystem of claim 12 wherein the therapeutic assembly further comprises aframe supporting the flexible membrane.
 14. The system of claim 1wherein: the distal portion of the shaft is transformable between alow-profile delivery state and an expanded state, the distal portion ofthe shaft has a spiral/helical shape when the distal portion of theshaft is in the expanded state, the one or more electrodes areconfigured to deliver radiofrequency (RF) energy to the target site, andthe distal portion of the shaft is configured to place at least one ofthe electrodes in direct contact with the target tissue at the targetsite when the distal portion of the shaft is in the expanded state. 15.The system of claim 1 wherein the therapeutic assembly comprises: aballoon transformable between a low-profile delivery state to anexpanded state; and a plurality of electrodes disposed on the balloon,wherein the plurality of electrodes are configured to deliverradiofrequency (RF) energy to the target site to therapeuticallymodulate parasympathetic nerves proximate to the target site.
 16. Thesystem of claim 15 wherein the balloon comprises a plurality of holesconfigured to allow perfusion of a fluid through the balloon when theballoon is in the expanded state.
 17. The system of claim 15, furthercomprising: a support extending through the balloon; and a plurality ofgraduated markings on at least one of the support or the balloon toidentify spatial positioning of the balloon.
 18. The system of claim 1wherein the therapeutic assembly comprises: a balloon transformablebetween a low-profile delivery state to an expanded state, wherein theballoon comprises a proximal cone portion; a return electrode on theballoon; and a flex circuit on the proximal cone portion, wherein thereturn electrode and the flex circuit are configured to deliverradiofrequency (RF) energy to the target site to therapeuticallymodulate parasympathetic nerves proximate to the target site.
 19. Thesystem of claim 1 wherein the therapeutic assembly comprises: aplurality of balloons extending distally from the distal portion of theshaft, wherein the balloons are independently expandable; and at leastone electrode on each of the balloons, wherein the electrodes areconfigured to deliver radiofrequency (RF) energy to the target site totherapeutically modulate parasympathetic nerves proximate to the targetsite.
 20. The system of claim 19, further comprising: an internalsupport member extending through a region between the balloons andconfigured to carry the balloons, wherein the internal support memberincludes a return electrode.
 21. The system of claim 1 wherein thetherapeutic assembly comprises a cryotherapeutic balloon configured toapply cryogenic cooling to tissue at the target site to therapeuticallymodulate autonomic activity.
 22. The system of claim 1 wherein thetherapeutic assembly comprises a balloon sized and shaped to contacttissue at the target state when expanded, and wherein the balloon isconfigured to circulate a fluid heated to at least 60° C. to thermallymodulate autonomic activity.
 23. The system of claim 1 wherein thetherapeutic assembly comprises: a balloon configured to be expanded witha fluid, wherein the balloon is sized and shaped to contact tissue atthe target state when expanded; and a heating member within the balloon,wherein the heating member is configured to heat the fluid in theballoon to thermally modulate autonomic activity.
 24. The system ofclaim 1 wherein the therapeutic assembly comprises a plasma ablationprobe.
 25. The system of claim 1 wherein: the plurality of struts form abasket configured to conform to adjacent anatomical structures andposition at least two of the electrodes in direct contact with thetarget tissue at the target site when the therapeutic assembly is in anexpanded state; the electrodes are configured to apply radiofrequency(RF) energy to the target site to block neural communication of thepostganglionic parasympathetic nerves at the target location; and thecontroller is configured to operate each electrode independently of theother electrode or electrodes, so that selective independent control ofthe electrodes enables the therapeutic assembly to deliver the RF energyto customized regions.
 26. The system of claim 25 wherein the measuredbioelectric properties include resistance of the target tissue at thetarget site.
 27. The system of claim 25 wherein the controller isconfigured to: cause the electrodes to measure the bioelectricproperties of the target tissue at the target site, wherein the targettissue includes heterogeneous tissue proximate to the target site; andidentify locations of the sphenopalatine foramen of the human patientand the target location of the postganglionic parasympathetic nervesinnervating the nasal mucosa at the microforamina of the palatine boneof the human patient, based on the measured bioelectric properties ofthe heterogeneous tissue.
 28. The system of claim 1 wherein thecontroller is configured to identify electrodes of the therapeuticassembly that are in direct contact with the target tissue at the targetsite, and selectively activate the identified electrodes totherapeutically modulate the postganglionic parasympathetic nerves. 29.The system of claim 1 wherein the controller is configured to identify aposition of the therapeutic assembly relative to the target site, andselectively activate the electrodes based on the position of thetherapeutic assembly relative to the target site.
 30. The system ofclaim 1 wherein, when selectively activated, the two or more electrodesin direct contact with the target tissue therapeutically modulate atleast one nerve at the target location within the target tissue.